Chemotherapy combined with immunotherapy in primary female urethral squamous cell carcinoma: a case report.
Primary female urethral carcinomas are uncommon and have a low morbidity rate. Most of these patients have advanced illness with high invasion and a poor prognosis. There is no standard treatment, and multimodal therapy is recommended. The use of radiotherapy and chemotherapy were mostly reported in previous studies on advanced female urethral squamous cell carcinoma. We report that chemotherapy combined with a programmed death-1 (PD-1) inhibitor was effective in treating metastatic female urethral squamous cell carcinoma. During four cycles, we used systemic chemotherapy of albumin-paclitaxel + carboplatin in combination with a PD-1 inhibitor (toripalimab 240 mg) every 3 weeks, and a complete response was achieved. We performed a genetic test on the patient who had a tumor mutation burden of 5.7 mutations/Mb, tumor proportion score of 20%, and combined positive score of 20% (22C3). No recurrence or distant metastasis was found after 20 months of follow-up. In conclusion, in patients with positive PD-1 ligand 1 expression in primary female urethral squamous cell carcinoma, chemotherapy combined with PD-1 inhibitors may be effective. Larger sample studies are required to determine PD-1 ligand 1 expression and the curative effect of PD-1 inhibitors, as well as their effect on survival.


White plague disease outbreak in a coral reef at Los Roques National Park, Venezuela.
Coral diseases have been reported as a major problem affecting Caribbean coral reefs. During August 2000, a coral mortality event of White Plague Disease-II (WPD-II) was observed at Madrizqui Reef in Los Roques National Park, Venezuela. This disease was identified as the major cause of coral mortality, affecting 24% of all colonies surveyed (n = 1 439). Other diseases such as Black Band Disease (BBD), Yellow Blotch Disease (YBD), Dark Spots Disease (DSD) and White Band Disease (WBD) were also recorded, but showed a lower incidence (0.14-0.97%). Two depth intervals, D1 (5.5-6.5 m) and D2 (9-9.5 m) were surveyed with two sets of three band transects 50 x 2 m long, placed parallel to the long axis of the reef. All healthy and injured corals, along each band transect, were counted and identified to species level. Additionally, all diseases and recent mortality that were still identifiable on each colony also were recorded. The incidence of colonies affected by WPD-II ranged from 12.8 to 33% among transects, where thirteen species of scleractinian corals showed several degrees of mortality. The species most affected were Montastraea annularis (39.13%), M. faveolata (26.67%), M. franksi (9.86%), Stephanocoenia intersepta (7.25%), Colpophyllia natans (6.96%), Diploria labyrinthiformis (2.99%), Mycetophyllia aliciae (2.03%), M. cavernosa (1.74%), and D. strigosa (1.45%). WPD-II was more common in the deeper strata (9-9.5 m), where 63% of the surveyed colonies were affected, although the disease was present along the entire reef. Presently, it is imperative to determine how fast the disease is spreading across the reef, how the disease spreads across the affected colonies and what the long-term effects on the reef will be.


[Selenium in mushrooms].
In the article are reviewed available data from the scientific literature on content as well as speciation of selenium in mainly edible mushrooms collected in Europe. Some species of the genus Albtrellus were found exceptionally rich in selenium, and relatively less are some representatives of the genus Boletus (especially Boletus eduilis), Macrolepiota, Agaricus or Ronmaria, while for many other is less than 1.0 mg/kg dry matters. Nevertheless, tha available database on selenium in higher edible mushrooms is not so great if considering the number of wild growing as well as cultivated species and their spread in space.


Impact of climate change on groundwater recharge in shallow young glacial aquifers in northern Poland.
We investigated the influence of climate change in the period 1951-2020 on shallow aquifers in the Brda and Wda outwash plains (Pomeranian Region, Northern Poland). There was a significant temperature rise (0.3 °C/10 years), which accelerated after 1980 (0.66 °C/10 years). Precipitation became increasingly irregular - extremely rainy years occurred right after or before extremely dry years, and intensive rainfall events became more frequent after 2000. The groundwater level decreased over the last 20 years, even though the average annual precipitation was higher than in the previous 50 years. We carried out numerical simulations of water flow in representative soil profiles for the years 1970-2020 using the HYDRUS-1D model, developed and calibrated during our earlier work at an experimental site in the Brda outwash plain (Gumuła-Kawęcka et al., 2022). We used a relationship between the water head and flux at the bottom of the soil profiles (the third-type boundary condition) to reproduce groundwater table fluctuations caused by recharge variability in time. The calculated daily recharge showed a decreasing linear trend for the last 20 years (0.05-0.06 mm d-1/10 years), and dropping trends in water table level and soil water content in the entire profile of vadose zone. Field tracer experiments were performed to estimate impact of extremely rain events on water flux in vadose zone. The results suggest that tracer travel times are strongly determined by water content in the unsaturated zone which is determined by precipitation amount in span of weeks, rather than extremely high precipitation events.


Spontaneous Remission of Acromegaly After Pituitary Apoplexy in a Middle-Aged Male.
Background: Pituitary apoplexy results from hemorrhage, infarction, or hemorrhagic infarction within a pituitary tumor. Subclinical or clinical apoplexy is not uncommon in acromegaly, owing to the large size of the tumor at initial detection. Growth hormone excess in acromegaly often persists following surgery. However, in rare instances, pituitary apoplexy may present a spontaneous cure to growth hormone excess. Case Report: A 40-year-old male presented with holocranial headache for the past 16 years that had worsened in severity during the prior year. Two months before presentation, he experienced a severe headache that he described as the worst headache of his life. The patient had prominent acromegaloid features that he ignored, as they seemed to cause no harm. The patient had no signs of clinically active disease. Magnetic resonance imaging of the brain revealed a pituitary macroadenoma with evidence of hemorrhage. Serum insulin-like growth factor 1 and oral glucose-suppressed serum growth hormone levels were normal, suggestive of inactive or silent disease. Pituitary apoplexy causing spontaneous remission of acromegaly was diagnosed, and close follow-up was planned for the evolution of hypopituitarism. Conclusion: This case highlights a rare presentation of acromegaly in which an episode of symptomatic pituitary apoplexy revealed the diagnosis of pituitary adenoma and led to the cure of growth hormone hypersecretion.


SIV replication in human cells.
Current human immunodeficiency virus type 1 pandemic is believed to originate from cross-species transmission of simian immunodeficiency virus (SIV) into human population. Such cross-species transmission, however, is not efficient in general, because viral replication is modulated by host cell factors, with the species-specificity of these factors affecting viral tropism. An understanding of those host cell factors that affect viral replication contributes to elucidation of the mechanism for determination of viral tropism. This review will focus an anti-viral effect of ApoB mRNA editing catalytic subunit, tripartite motif protein 5 alpha, and cyclophilins on SIV replication and provide insight into the mechanism of species-specific barriers against viral infection in human cells. It will then present our current understanding of the mechanism that may explain zoonotic transmission of retroviruses.


[Health-economic considerations for the use of BMP-2 for spinal surgery in Germany].
BMP-2 can replace autogenous bone grafting in lumbar one-level anterior lumbar interbody fusions (ALIF). The current G-DRG system does not reimburse the upfront price of 2,970 euro per BMP-2 application for hospitals in Germany. The purpose of the current study was to create a health economic model to evaluate the financial savings for health care providers (hospitals) and health care payers (health care insurance) that can be achieved by the use of BMP-2 in spine surgery. A previously published pooled data analysis was used in which BMP-2 showed significant improvements in the treatment after ALIF surgery compared to autogenous bone grafting, including earlier return to work time and reduced revision rates. These medical findings were transformed into economic data based on the regulations of the German health system of 2005. The significantly shorter return to work time under BMP-2 treatment generates important financial savings for health care insurances offsetting the upfront prize of 2,970 euro for BMP-2. Savings for hospitals are mainly related to shorter surgery time due to the absence of the bone grafting procedure and faster discharge of the patient. The combination of improved medical outcome by BMP-2 treatment for the patient and net savings for the entire health care system in Germany represents a "dominant" strategy from a health economic perspective. This implicates that BMP-2 in ALIF procedures is to be recommended from a health economic point of view for the German health care system.


[Clinical efficacy of ladder neoadjuvant therapy in treatment of advanced mid-low rectal cancer].
Objective: To explore the clinical efficacy of ladder neoadjuvant therapy in treatment of advanced mid-low rectal cancer. Methods: We performed a retrospective study of one hundred and eighty mid and low rectal cancer patients who underwent ladder neoadjuvant therapy(neoadjuvant chemotherapy followed by surgery if neoadjuvant chemotherapy was effective; neoadjuvant chemotherapy followed by neoadjuvant chemoradiotherapy if neoadjuvant chemotherapy was ineffective)(n=90) or neoadjuvant chemoradiotherapy (n=90). Results: In the ladder neoadjuvant therapy group, the descent stage rate was 85.6% (77/90), the anastomosis rate was 50.0% (45/90), the pre-sacral infection rate was 4.4% (4/90), the pathological complete remission (pCR) was 13.3%(12/90), R0 resection rate was 85.6% (77/90), the 2-year disease control rate was 76.7% (69/90), and the 2-year survival rate was 90.0% (81/90). In the control group, the descent stage rate was 88.9% (80/90), The anastomosis rate was 45.6% (41/90), the rate of pre-sacral infection was 11.1% (10/90), pCR was 16.7% 15/90), R0 resection rate was 88.9% (80/90), the 2-year disease control rate was 78.9% (71/90), and the 2-year survival rate was 87.8% (79/90). The difference was not statistically significant (P>0.05). The ladder neoadjuvant therapy group had lower prophylactic transverse colostomyrate(10.0% vs 34.4%), lower radiation injury rate (6.7% vs 27.8%), and lower sexual dysfunction rate (38.9% vs 87.8)compared to the control group. Conclusions: The ladder neoadjuvant therapy might reduce side injury caused by radiotherapy, improve compliance of patients, and reduce treatment costs. Moreover, the RO resection rate, 2-year local control rate and 2-year survival rate of ladder neoadjuvant therapy group was comparable with neoadjuvant chemoradiotherapy.


Norfloxacin in the treatment of infections caused by Salmonella typhi.
The bacteriological and clinical efficacy of norfloxacin 400 mg b.i.d. was studied in an open, non-comparative trial. Twenty-seven patients with clinical symptoms of typhoid fever were included and assigned to treatment for 14 days. Salmonella typhi was found in stools and/or blood cultures from 12 patients. Subsequent cultures from ten of these patients were negative during treatment and in the follow-up period. Two patients remained positive in stool cultures. Body temperature normalized within one week in 11 of the 12 evaluable patients. In conclusion, these results indicate the potential clinical value of norfloxacin for treatment of typhoid fever. Further controlled and comparative studies are needed.


Thermal E/ Z Isomerization in First Generation Molecular Motors.
Determination of a thermal E/ Z isomerization barrier of first generation molecular motors is reported. Stable ( E)-1a directly converts to stable ( Z)-1c without photochemical E/ Z isomerization. The activation Gibbs energy of the isomerization was determined to be 123 kJ mol-1 by circular dichroism spectral changes. Density functional theory calculations show that ( Z)-1c is ∼11.4 kJ mol-1 more stable than ( E)-1a.


Nuclear competence for maturation and pronuclear formation in mouse oocytes.
In response to gonadotrophins, a fully grown mouse oocyte matures to the metaphase of the second meiotic division and becomes competent for the development of female and male pronuclei after fertilization. The present study was carried out to clarify when during the growth period an oocyte nucleus acquires the ability to promote pronuclei formation after fertilization. Fully grown germinal vesicle (GV) oocytes were enucleated and fused with nuclei from growing oocytes from 1-20 day old mice by standard nuclear transfer technique. The reconstructed oocytes were matured and fertilized in vitro, and pronuclear formation was assessed. The oocytes whose nuclei were exchanged for those of the non-growing-stage oocytes matured to the metaphase of the second meiotic stage, but no normal female pronuclei were formed. Female pronuclei first formed in 27% of the oocytes reconstituted with the nuclei of oocytes from 8 day old pups after fertilization. Recondensed sperm chromatin was detected in 27% of the oocytes reconstructed with oocyte nuclei from 8 day old mice, and a male pronucleus was first formed in 6% of the oocytes that had been reconstructed with the nuclei of oocytes from 15 day old mice. The sizes of the female and male pronuclei increased with oocyte donor age, and reached normal size when the oocytes from 15 and 20 day old mice respectively were used. An electron microscopic study using oocytes that had received the oocyte nuclei of 8 day old mice confirmed these results. The factors required for pronuclear formation are derived from fully grown GV oocytes, and the transformation from decondensed sperm chromatin to a recondensed male pronucleus is governed by GV-derived factors.


Synthesis and SAR studies for the inhibition of TNF-alpha production. Part 2. 2-[3-(Cyclopentyloxy)-4-methoxyphenyl]-substituted-1-isoindolinone derivatives.
This study describes the synthesis and in vitro evaluation of 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of TNF-alpha production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-amino-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in inhibitory activity of TNF-alpha production in LPS-stimulated RAW264.7 cells.


Inhibition of sperm motility by bovine serum components.
Various sources and components of mammalian sera were evaluated for their ability to maintain or inhibit sperm motility. Human, rabbit, hamster, and porcine sera were equal in ability to maintain motility of human sperm. Four sources of fetal calf serum and one source of neonatal calf serum were unable to maintain motility of human sperm or sperm-fertilizing potential. In the presence of human serum, fetal calf serum actually inhibited human sperm motility. Fetuin, a component of fetal calf serum, contained the inhibitory activity. An inhibitory effect of fetuin on porcine and caprine sperm motility was also observed. The inhibitory activity resided in the second peak when fetuin was separated by isoelectric focusing. The sperm head membranes remained impermeable to dye, and mitochondrial membrane potential was maintained after motility had been reduced to almost zero by incubation with fetuin and fetuin fractions. Fetuin or the active portion of the molecule may be a useful component of a vaginal contraceptive and in research where inhibition of motility is desirable.


Symbiotic Self-Assembly Strategy toward Lipid-Encased Cross-Linked Polymer Nanoparticles for Efficient Gene Silencing.
A novel "symbiotic self-assembly" strategy that integrates the advantages of biocompatible lipids with a structurally robust polymer to efficiently encapsulate and deliver siRNAs is reported. The assembly process is considered to be symbiotic because none of the assembling components are capable of self-assembly but can form well-defined nanostructures in the presence of others. The conditions of the self-assembly process are simple but have been chosen such that it offers the ability to arrive at a system that is noncationic for mitigating carrier-based cytotoxicity, efficiently encapsulate siRNA to minimize cargo loss, be effectively camouflaged to protect the siRNA from nuclease degradation, and efficiently escape the endosome to cause gene knockdown. The lipid-siRNA-polymer (L-siP) nanoassembly formation and its disassembly in the presence of an intracellular trigger have been extensively characterized experimentally and through computational modeling. The complexes have been evaluated for the delivery of four different siRNA molecules in six different cell lines, where an efficient gene knockdown is demonstrated. The reported generalized strategy has the potential to make an impact on the development of a safe and effective delivery agent for RNAi-mediated gene therapy that holds the promise of targeting several hard-to-cure diseases.


Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.
Chronic pulmonary aspergillosis (CPA) is a devastating disease with increasing prevalence worldwide. The characteristic granulomatous-like inflammation poses as the major setback to effective antifungal therapies by limiting drug access to fungi. These inflammatory lung structures are reported to be severely hypoxic; nevertheless, the underlying mechanisms whereby these processes contribute to fungal persistence remain largely unknown. Hypoxia-inducible factor 1 alpha (HIF-1α), besides being the major cellular response regulator to hypoxia, is a known central immune modulator. Here, we used a model of Aspergillus fumigatus airway infection in myeloid-restricted HIF-1α knock-out (mHif1α-/- ) mice to replicate the complex structures resembling fungal granulomas and evaluate the contribution of HIF-1α to antifungal immunity and disease development. We found that fungal-elicited granulomas in mHif1α-/- mice had significantly smaller areas, along with extensive hyphal growth and increased lung fungal burden. This phenotype was associated with defective neutrophil recruitment and an increased neutrophil death, therefore highlighting a central role for HIF-1α-mediated regulation of neutrophil function in the pathogenesis of chronic fungal infection. These results hold the promise of an improved capacity to manage the progression of chronic fungal disease and open new avenues for additional therapeutic targets and niches of intervention.


Women and the fear of being envied.
Nursing is very much concerned with the health and status of women. Perhaps at the same time we are attempting to work therapeutically with this very large portion of humankind, it would be beneficial for us to more closely analyze our own difficulties as a profession made up almost exclusively of women. What is the relationship between the level of our self-esteem and our problem with envy--envy of and fear of being envied by other nurses and health care providers? In terms of professional achievement, to what extent is fear of success related to fear of being envied? Lastly, if we open the affective windows and allow some honest dialogue to blow through about a subject we tend to repress, will we be able to outgrow our "one-down" position?


Prototypical versus contemporary Mediterranean Diet.
To investigate the evolution of the Mediterranean Diet (MD) in a delimited area of Southern Italy, by comparing the diet adopted 60-70 years ago (Prototypical Mediterranean Diet, PMD) with the contemporary one (Contemporary Mediterranean Diet, CMD), and to verify to what extent they fitted the recommendations of the Italian and the USDA dietary guidelines. We recruited a total of 106 participants, divided in two groups. PMD group included 52 women aged >80 years, with a good cognitive function and full independence in basic and instrumental activities of daily living. CMD group included 20 men and 34 women aged 50-60 years. Food intake was assessed by administering the EPIC food frequency questionnaire to each participant, and an additional survey to the PMD subjects only. Both PMD and CMD showed adequate intakes of macronutrients, although some deficiencies related to micronutrient requirements were evident. CMD showed a slightly greater use of animal products, processed and sugary foods, and higher intakes of simple sugars, animal proteins (49.6 vs 28.3 g/day), animal lipids (37.8 vs 20.1 g/day), saturated fats (25.0 vs 15.8 g/day) and cholesterol (305.0 vs 258.5 g/day). PMD showed many similarities to the original version of the MD in terms of macronutrients distribution and food choices. The documented evolution of the dietary habits over a 70 years timespan suggests that nowadays Mediterranean regions adhere less strictly to the original MD, although nutrients intakes are adequate to LARN and USDA recommendations.


Continental impacts of water development on waterbirds, contrasting two Australian river basins: Global implications for sustainable water use.
The world's freshwater biotas are declining in diversity, range and abundance, more than in other realms, with human appropriation of water. Despite considerable data on the distribution of dams and their hydrological effects on river systems, there are few expansive and long analyses of impacts on freshwater biota. We investigated trends in waterbird communities over 32 years, (1983-2014), at three spatial scales in two similarly sized large river basins, with contrasting levels of water resource development, representing almost a third (29%) of Australia: the Murray-Darling Basin and the Lake Eyre Basin. The Murray-Darling Basin is Australia's most developed river basin (240 dams storing 29,893 GL) while the Lake Eyre Basin is one of the less developed basins (1 dam storing 14 GL). We compared the long-term responses of waterbird communities in the two river basins at river basin, catchment and major wetland scales. Waterbird abundances were strongly related to river flows and rainfall. For the developed Murray-Darling Basin, we identified significant long-term declines in total abundances, functional response groups (e.g., piscivores) and individual species of waterbird (n = 50), associated with reductions in cumulative annual flow. These trends indicated ecosystem level changes. Contrastingly, we found no evidence of waterbird declines in the undeveloped Lake Eyre Basin. We also modelled the effects of the Australian Government buying up water rights and returning these to the riverine environment, at a substantial cost (>3.1 AUD billion) which were projected to partly (18% improvement) restore waterbird abundances, but projected climate change effects could reduce these benefits considerably to only a 1% or 4% improvement, with respective annual recovery of environmental flows of 2,800 GL or 3,200 GL. Our unique large temporal and spatial scale analyses demonstrated severe long-term ecological impact of water resource development on prominent freshwater animals, with implications for global management of water resources.


p21, p27 and p53 in estrogen and antiprogestin-induced tumor regression of experimental mouse mammary ductal carcinomas.
Metastatic mammary carcinoma tumor lines 59-2-HI and C7-2-HI originated in female BALB/c mice treated with medroxyprogesterone acetate and are maintained by syngeneic transplantation. Both lines express estrogen (ER) and progesterone receptors (PR) and regress completely after estradiol (E(2)) or antiprogestin treatment. The BET tumor line, of similar origin and biological features, regresses only after E(2) treatment. To investigate possible differences between E(2)- and antiprogestin-mediated effects we evaluated the morphological features, mitosis and apoptosis, and the differential expression of cell-cycle inhibitors associated with tumor regression. Treatments started when tumors reached 50-100 mm(2). After 24-96 h, tumors were excised and processed for morphological and immunohistochemical studies. Regression was associated with a significant and early decrease in the number of mitosis and with higher percentages of apoptotic cells. These phenomena were accompanied by an increase in p21 and p27 expression in the E(2) and antiprogestin-responsive lines treated with E(2), RU 38.486 or ZK 98.299 (P < 0.05). In BET tumors treated with E(2), p21 expression remained within basal levels and only p27 increased (P < 0.05). p53 was low in control 59-2-HI and C7-2-HI tumors and increased after treatment (P < 0.05) whereas BET untreated tumors already expressed high levels of p53 and MDM2. Although the immunohistochemical findings were compatible with alterations of p53, SSCP evaluation failed to disclose the presence of mutations, suggesting that the defective expression of p21 is related to an impaired p53 pathway. UV irradiation failed to increase p21 expression in BET, but was able to induce p53 and p21 in 59-2-HI and C7-2-HI tumors. The absence of an increased expression of p21 in E(2)-regressing BET lesions suggests that this protein is not necessary for estrogen-induced regression, but may be essential for antiprogestin action. Our results also suggest that p53/MDM2 alterations may be one of the mechanisms responsible for selected hormone resistance in breast carcinomas.


Obesity and high neutrophil-to-lymphocyte ratio are prognostic factors in non-metastatic breast cancer patients.
Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.


[Pelvic morphology and lumbar spondylolisthesis].
Pelvic morphology is involved in the genesis of spondylolisthesis. The mean age of patients with spondylolisthesis was 57.9 +/- 9.5 years (40-81). 14 were complaining of low back pain and 12 had sciatica. Spondylolisthesis was in stage 1 in 75% of the cases and in stage 2 in 25% of the cases. Low lordosis was observed in patients and controls in 73% and 100% of the cases respectively. Sacral slops was slightly higher in patients than in controls and was higher than 40 degrees in patients and controls at a rate of 35% and 25% respectively. The incidence was higher in patients than in controls. There was a high pelvic retroversion in patients than in controls. High incidence and pelvic retroversion were found in patients with spondylolisthesis and pelvic morphology was probably involved in the genesis of spondylolisthesis.


Stability of Crushed Tedizolid Phosphate Tablets for Nasogastric Tube Administration.
Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infections. To determine whether the expected dose of tedizolid phosphate can be delivered via nasogastric tube in patients who have difficulty swallowing and in whom venous access is not suitable, this in vitro study evaluated the recovery of tedizolid phosphate 200-mg tablets after crushing, dispersion in water, and passage through a nasogastric tube. To analyze the chemical stability of the crushed tablet dispersed in water, the aqueous preparation was assayed initially after dispersion and again after 4 h at room temperature. Recovery of tedizolid phosphate after the crushed tablets were dispersed in water and passed through nasogastric tubes ranged from 92.5 to 97.1 %, which is within the specified acceptance criteria of 90 to 110 %. There was no significant change in recovery values after 4 h of storage at room temperature (93.9 % initially and 94.7 % after 4 h). The stability and recovery findings support the feasibility of administering an aqueous dispersion of crushed tedizolid phosphate tablets through a nasogastric tube in patients who have difficulty swallowing and in whom intravenous administration is not possible.


Carbon nanotubes for microelectronics?
Despite all prophecies of its end, silicon-based microelectronics still follows Moore's Law and continues to develop rapidly. However, the inherent physical limits will eventually be reached. Carbon nanotubes offer the potential for further miniaturization as long as it is possible to selectively deposit them with defined properties.


Experimental cold injury to peripheral nerve.
Focal non-freezing injury to rat sciatic nerve resulted in nerve conduction block and cessation of axoplasmic transport. Rats showed early functional recovery but subsequently developed a slowly progressive sciatic nerve paralysis. Horseradish peroxidase studies revealed prominent nerve oedema with early enhanced pinocytosis and later, passive leakage through damaged endoneurial capillaries. Detailed microscopy indicated a striking selective vulnerability to cold based on nerve fibre diameter. Unmyelinated fibres were spared while large myelinated nerve fibres showed severe axonal degeneration. Paranodal and segmental demyelination were infrequent findings and may have resulted from early axonal swelling. Possible pathogenic mechanisms to explain the degeneration of myelinated fibres in hypothermic injury are discussed. It is concluded that the gradient of clinical severity seen in limb hypothermic injuries has a pathological correlate in peripheral nerve.


Microbiological Evaluation of Household Drinking Water Treatment in Rural China Shows Benefits of Electric Kettles: A Cross-Sectional Study.
In rural China ~607 million people drink boiled water, yet little is known about prevailing household water treatment (HWT) methods or their effectiveness. Boiling, the most common HWT method globally, is microbiologically effective, but household air pollution (HAP) from burning solid fuels causes cardiovascular and respiratory disease, and black carbon emissions exacerbate climate change. Boiled water is also easily re-contaminated. Our study was designed to identify the HWT methods used in rural China and to evaluate their effectiveness. We used a geographically stratified cross-sectional design in rural Guangxi Province to collect survey data from 450 households in the summer of 2013. Household drinking water samples were collected and assayed for Thermotolerant Coliforms (TTC), and physicochemical analyses were conducted for village drinking water sources. In the winter of 2013-2104, we surveyed 120 additional households and used remote sensors to corroborate self-reported boiling data. Our HWT prevalence estimates were: 27.1% boiling with electric kettles, 20.3% boiling with pots, 34.4% purchasing bottled water, and 18.2% drinking untreated water (for these analyses we treated bottled water as a HWT method). Households using electric kettles had the lowest concentrations of TTC (73% lower than households drinking untreated water). Multilevel mixed-effects regression analyses showed that electric kettles were associated with the largest Log10TTC reduction (-0.60, p<0.001), followed by bottled water (-0.45, p<0.001) and pots (-0.44, p<0.01). Compared to households drinking untreated water, electric kettle users also had the lowest risk of having TTC detected in their drinking water (risk ratio, RR = 0.49, 0.34-0.70, p<0.001), followed by bottled water users (RR = 0.70, 0.53-0.93, p<0.05) and households boiling with pots (RR = 0.74, 0.54-1.02, p = 0.06). As far as we are aware, this is the first HWT-focused study in China, and the first to quantify the comparative advantage of boiling with electric kettles over pots. Our results suggest that electric kettles could be used to rapidly expand safe drinking water access and reduce HAP exposure in rural China.


A case of marked hyperlipoprotein(a)emia associated with nephrotic syndrome and advanced atherosclerosis.
In 1989, we encountered a 68-year-old male patient with marked hyperlipoprotein(a)emia (hyperLp(a)emia), who was being treated for hypertension and arteriosclerotic obliterans (ASO) at an outpatient clinic of our hospital. He began to develop leg edema in 2002 and was referred to the Department of Internal Medicine. It was determined that he had severe hyperlipidemia (total cholesterol, 362 mg/dl), proteinuria, and hypoalbuminemia, suggesting the presence of nephrotic syndrome. On lipoprotein analysis, he was found to have very high levels of Lp(a) in the plasma (329 mg/dl). Severe atherosclerosis was also found: that is, abdominal aortic aneurysm (AAA) and coronary artery disease (CAD) were detected, in addition to ASO. After remission of the nephrotic syndrome, the plasma Lp(a) level decreased to 204 mg/dl and the total cholesterol concentration decreased to 179 mg/dl, while very high levels of Lp(a) persisted. We estimate that the markedly elevated Lp(a) plasma levels in this patient may have played some role in the progression of atherosclerosis.


Morphometric Assessment of Facial Morphology in Infants with Orofacial Clefts up to two Years of Age: A Three-Dimensional Cross-Sectional Study.
To assess modelled facial development of infants with unilateral cleft lip (CL) and cleft lip and palate (UCLP) compared to controls up to two years of age. A total of 209 facial images of children (CL: n = 37; UCLP: n = 39; controls: n = 137) were obtained in four age categories (T0 = 0.2-0.5; T1 = 0.6-1.0; T2 = 1.1-1.5; T3 = 1.6-2.0 years) and were evaluated using stereophotogrammetry and geometric morphometry. All patients underwent lip surgery before T0, patients with UCLP underwent palatoplasty (T0, T1 before palatoplasty; T2, T3 after palatoplasty). In patients with CL, the forehead was significantly retracted (p ≤ 0.001), while the supraorbital and ocular regions were prominent (p ≤ 0.001). The oronasal region appeared convex (p ≤ 0.001). The lower lip and chin were non-significantly protruded. In patients with UCLP, a significantly retracted forehead and prominent supraorbital region were apparent (p ≤ 0.001). A retrusive oronasal region (p ≤ 0.001) was observed in the middle face. The chin was anteriorly protruded (p ≤ 0.01). No progression of deviations was found with increasing age. After the first year, a slight improvement in the morphological features became apparent. The shape variability of the clefts and controls overlapped, suggesting a comparable modelled facial development. The facial morphology of individuals with cleft was comparable to the norm. Shape deviation was apparent in the oronasal region, forehead, and chin, which minimised with increasing age even in complete clefts.


Substitution of dietary ω-6 polyunsaturated fatty acids for saturated fatty acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia associated with insulin resistance: a randomized controlled trial.
The substitution of omega (ω)-6 (n-6) polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) is advocated in cardiovascular disease prevention. The impact of this substitution on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains unknown. In men with dyslipidemia and IR, we evaluated the impact of substituting ω-6 PUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo) B-containing lipoproteins and on the intestinal expression of key genes involved in lipoprotein metabolism. Dyslipidemic and IR men (n = 36) were recruited for this double-blind, randomized, crossover, controlled trial. Subjects consumed, in a random order, a fully controlled diet rich in SFAs (SFAs: 13.4% of energy; ω-6 PUFAs: 4.0%) and a fully controlled diet rich in ω-6 PUFAs (SFAs: 6.0%; ω-6 PUFAs: 11.3%) for periods of 4 wk, separated by a 4-wk washout period. At the end of each diet, the in vivo kinetics of apoB-containing lipoproteins were measured and the intestinal expression of key genes involved in lipoprotein metabolism was quantified in duodenal biopsies taken from each participant. The substitution of ω-6 PUFAs for SFAs had no impact on TRL apoB-48 fractional catabolic rate (Δ = -3.8%, P = 0.7) and production rate (Δ = +1.2%, P = 0.9), although it downregulated the intestinal expression of the microsomal triglyceride transfer protein (Δ = -18.4%, P = 0.006) and apoB (Δ = -16.6%, P = 0.005). The substitution of ω-6 PUFAs for SFAs decreased the LDL apoB-100 pool size (Δ = -7.8%; P = 0.005). This difference was attributed to a reduction in the LDL apoB-100 production rate after the substitution of ω-6 PUFAs for SFAs (Δ = -10.0%; P = 0.003). This study demonstrates that the substitution of dietary ω-6 PUFAs for SFAs decreases the production and number of LDL particles in men with dyslipidemia and IR. This trial was registered at clinicaltrials.gov as NCT01934543.


Ornithine decarboxylase (ODC) expression pattern in human prostate tissues and ODC transgenic mice.
Ornithine decarboxylase (ODC) is the key enzyme in the polyamine synthesis pathway and is overexpressed in a variety of cancers. We have performed a detailed immunostaining analysis of the expression of ODC in normal, benign prostatic hyperplasia (BPH), and cancerous prostate tissues. We conclude that ODC is overexpressed in both BPH and neoplastic tissues and that ODC overexpression appears to be an early event in prostate carcinogenesis. The extent of overexpression decreases as cancer progresses. Interestingly, ODC overexpression was also detected in patients who underwent androgen ablation therapy, suggesting ODC overexpression may contribute to the androgen-independent survival of prostate cancer cells. ODC is perinuclear localized in BPH samples but is diffusely cytoplasmic in cancer samples. Having shown ODC overexpression in human prostate cancer, we developed prostate-specific ODC transgenic mice to further investigate whether ODC overexpression alone is a causal factor in prostate carcinogenesis. RT-PCR and immunostaining confirmed that ODC was overexpressed in a subset of prostate epithelial cells. Although minor nucleoli enlargements in some tissues were detected, gross morphological changes were not observed in transgenic prostates. Therefore, overexpression of ODC alone in this subset of prostate epithelial cells is not sufficient to induce prostate carcinogenesis.


Multi-modality treatment of primary nonresectable intrahepatic cholangiocarcinoma with 131I anti-CEA--a Radiation Therapy Oncology Group Study.
Thirty-seven patients with primary nonresectable intrahepatic cholangiocarcinoma (57% with prior treatment and/or metastasis) were prospectively treated with external radiation, chemotherapy, and 131I labelled anti-CEA. Therapy began in all trials with whole liver irradiation (21.0 Gy, 3.0 Gy/Fx, 4 days/week, 10 MV photons) with alternate treatment day chemotherapy (Adriamycin, 15 mg + 5-FU, 500 mg). One month after external beam therapy, chemotherapy was given (Adriamycin, 15 mg + 5-FU, 500 mg) followed the next day by the first administration of 131I anti-CEA. The treatment schedule used was 20 mCi day 0; 10 mCi day 5 as an outpatient. This schedule was derived from tumor dose estimates which indicated that 20 mCi (8-10 mCi/mg IgG) was sufficient to achieve tumor saturation with a tumor effective half-life of 3 to 5 days, depending upon the species of animal from which the antibody was obtained. The median tumor dose for the 20 mCi + 10 mCi regimen was 6.2 Gy. Antibody therapy was delivered in 2-month cycles using antibody generated in different species of animals; rabbit, pig, monkey, and bovine. Toxicity was limited to hematologic toxicity and was manifested as thrombocytopenia and leukocytopenia (3.2% Grade IV for each according to RTOG toxicity criteria). Tumor remission evaluated by CT scan digitized tumor volume analysis indicated a 26.6% partial response (PR). Tumor remission by physical examination indicated a 33.3% remission rate (25.9% PR and 7.4% complete remission (CR]. The median survival for patients who responded was 15.2 months. The actuarial median survival for the entire group of patients (metastases and previous treatment) was 6.5 months. The longest partial remission is presently more than 4 years.


Neurological manifestations in dogs naturally infected by Leishmania infantum: descriptions of 10 cases and a review of the literature.
In order to evaluate possible nervous system involvement in canine leishmaniasis, retrospective evaluation of all medical records of leishmaniotic dogs exhibiting neurological signs referred to our hospital over a 5-year period was performed. The records of 10 dogs were reviewed. Depending on the neuroanatomical localisation, the dogs underwent advanced diagnostic imaging, cerebrospinal fluid analysis, electrodiagnostic testing and histopathologic evaluations. The final neurological diagnosis was: meningoencephalitis (n=2), brain haemorrhagic stroke (n=1), haemorrhagic choroiditis (n=1), meningomyelitis (n=2), ischaemic myelopathy (n=1), polymyositis (n=2) and peripheral neuropathy (n=1). This study confirms that both central and peripheral nervous systems can be affected by leishmaniasis and provides an overview on the possible etiopathogenetic mechanisms. In addition, clinical and diagnostic findings, therapy and follow-up of affected dogs are described.


Multifocal Lupus Vulgaris: A Rare Presentation.
Lupus vulgaris (LV) is a common type of cutaneous tuberculosis and commonly presents as a single erythematous plaque either on the face or buttocks with scarring and an active spreading edge. Multiple lesions of LV are sparingly reported in the literature. We hereby report a case of LV in a male presenting with multiple lesions over the buttock, thigh, and trunk. The diagnosis was done on the basis of clinical findings, histopathology, positive tuberculin test, and response to a standard anti-tubercular regimen.


Healthcare employers' policies on nurse education.
The 2010 recommendation that the proportion of registered nurses with BSN (bachelor of science in nursing) degrees in the nursing workforce should increase from the current 40% to 80% by the year 2020 has shifted the focus on nurses educational progression from state legislatures-where changes in entry-level requirements were debated for decades-to the executive suites of large healthcare providers. The recommendation, contained in the report titled The Future of Nursing: Leading Change, Advancing Health, by the Robert Wood Johnson Foundation Initiative on the Future of Nursing at the Institute of Medicine, suggests that human resources policies for nurses have the potential to double the rates of college degree completions (IOM, 2010). We surveyed 447 nurse executives in hospitals, nurse-led clinics, and home and hospice companies to explore the current practices of healthcare employers with regard to this recommendation. Almost 80% of respondents reported that their institution either preferred or required newly hired nurses to have a bachelor's degree, and 94% of the facilities offered some level of tuition reimbursement. Only 25%, however, required their nurses to earn a BSN or offered salary differentials on the basis of educational attainment (9%). We conclude that if employers are serious about wanting a more highly educated nurse workforce, they need to adopt requirements for degree completion and wage differentials in the coming years. The likelihood that such policies will be widely adopted, however, is dramatically affected by the dynamics of nursing supply and demand.


Endangered light-footed clapper rail affects parasite community structure in coastal wetlands.
An extinction necessarily affects community members that have obligate relationships with the extinct species. Indirect or cascading effects can lead to even broader changes at the community or ecosystem level. However, it is not clear whether generalist parasites should be affected by the extinction of one of their hosts. We tested the prediction that loss of a host species could affect the structure of a generalist parasite community by investigating the role of endangered Light-footed Clapper Rails (Rallus longirostris levipes) in structuring trematode communities in four tidal wetlands in southern California, U.S.A. (Carpinteria Salt Marsh, Mugu Lagoon) and Mexico (Estero de Punta Banda, Bahia Falsa-San Quintin). We used larval trematode parasites in first intermediate host snails (Cerithidea californica) as windows into the adult trematodes that parasitize Clapper Rails. Within and among wetlands, we found positive associations between Clapper Rails and four trematode species, particularly in the vegetated marsh habitat where Clapper Rails typically occur. This suggests that further loss of Clapper Rails is likely to affect the abundance of several competitively dominant trematode species in wetlands with California horn snails, with possible indirect effects on the trematode community and changes in the impacts of these parasites on fishes and invertebrates.


Association between cholinesterase's inhibition and cognitive impairment: A basis for prevention policies of environmental pollution by organophosphate and carbamate pesticides in Chile.
In Chile organophosphate pesticides are widely used in the production of fruits. Pesticides use is regulated for professional practice but there is no regulation regarding exposure to the general population. To relate exposure to cholinesterase's inhibitor pesticides during the spray season with neuropsychological impairment in occupationally exposed (OE) and environmentally exposed (EE) groups of people. Exposure was assessed through inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity and neuropsychological outcomes were evaluated through a large battery of tests covering general mental status, language, memory, attention, executive function, praxis and psychomotricity. Evaluations were carried out firstly in a period of no/low organophosphate pesticide use and subsequently during the spray season. All parameters were calculated as the relative change from baseline to spray season. For this study in total 156 participants were recruited divided equally over participants with environmental exposures (EE) and participants with occupational exposure (OE). In the EE, BChE's enzyme activity inhibition ≥30% showed significant association with 10% or more decreased performance in several tests evaluating six of the eight cognitive areas (excepting psychomotricity and mood status); besides, for AChE inhibition in EE, the association was significant in three tests evaluating attention and one of executive function. Whereas, in OE, the inhibition of the BChE ≥30% was associated with a low performance of one attention test and for AChE the exceedance of the standard was associated with diminished performance in one test of memory and attention, respectively. The association between biomarkers of biological effect and cognitive impairment persisted among the EE group after removing confounders. No association was found between biomarkers of biological acute effect and decreased cognitive performance in the OE group. Increased exposure to pesticides was confirmed by increased inhibition of cholinesterase's in both exposure groups; which was associated with a diminished neuropsychological performance, mainly in the environmentally exposed study group. [310 words].


Building and Testing of a Conceptual Model to Describe and Measure the Health of People as Affected by Post-traumatic Stress Disorder During Social Unrest: A Confirmatory Factor Analysis and Structural Equation Modeling.
Social unrest affects people's health and well-being. People's health-related needs during social unrest are concerns in both research and clinical practice. This study aimed to build and test a framework to describe and understand the health status and needs of people with post-traumatic stress disorder (PTSD) during social unrest. This study was a cross-sectional survey. A total of 460 people who had experienced post-traumatic distress as a result of the social unrest in 2019 and 2020 were included. A conceptual model comprised four essential areas, namely posttraumatic distress symptoms, participation restrictions, perceived stigma and functional disability, was built from literature. Part 1 validated four instruments that evaluate and define the factor structure of these four areas, In Part II, structural equation modeling was used to test and validate a combined model. Factors underlying the four areas were defined. Analysis using structural equation modeling confirmed a best fit of the model. PTSD symptoms, perceived stigma and participation restriction during social unrest contributed significantly to functional disability; PTSD symptoms exerted a direct effect on participation restriction and perceived stigma; and the effect of PTSD symptoms on functional disability was mediated through its influence on perceived stigma during social unrest. A community-based inclusive approach is essential to understand the holistic needs of people with PTSD during social unrest. To improve health and well-being in addition to evaluating mental health impacts, considering interactions with the rapid change and stressful social environment is essential.


Psychiatric disorders among foreign-born and US-born Asian-Americans in a US national survey.
Among Hispanics, Non-Hispanic Whites and Non-Hispanic Blacks studies have found lower risk for psychiatric disorders among the foreign-born than among the US-born. We examine the association of nativity and risk for psychiatric disorder in a national sample of the Asian-American (AA) population. Data on 1,236 AAs from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) are analyzed using logistic regression and discrete time survival models to specify differences between the foreign-born and US-born in the lifetime occurrence of mood, anxiety and substance use disorders. Foreign-born AAs had significantly lower risk for all classes of disorder compared with US-born AAs (OR = 0.16-0.59). Risk for all classes of disorder was lowest for those foreign-born AAs who arrived in the US as adults. Among foreign-born AAs risk of first onset was lowest relative to the US-born in years prior to their arrival in the US and tended to rise to levels equal to that of the US-born with longer duration of residence in the US. Among AAs, risk for psychiatric disorders is lower among the foreign-born than among the US-born. The pattern of change in risk over time suggests that both the developmental timing and the duration of experience in the US contribute to increases in risk.


Benign inoperable tracheal stenosis in COVID versus non-COVID patients at the pandemic epicenter: a case series.
The COVID-19 pandemic has exponentially expanded the number of patients requiring treatment for chronic respiratory failure. One consequence is an increase in the number of patients requiring intubation and mechanical ventilation. Benign inoperable tracheal stenosis presents a challenge, especially in COVID-19 patients. We describe a case series of 15 patients with Benign inoperable tracheal stenosis treated with interventional bronchoscopy over a 15-month period. These patients were divided into two groups, COVID and non-COVID. We used an electrocautery snare as an electrocautery knife to cut the stenotic segment followed by four injections of 1 mg submucosal Decadron via a Wang needle. Patients were subsequently followed by the pulmonary clinic. Institutional review board approval was not required as per our institutional policy for a retrospective case series. There was a high degree of success with this intervention, with a low rate of recurrence. We also noticed the following differences between the two subgroups. COVID tracheal stenosis was longer in length, had a higher percentage of cartilage involvement, and was located more distal to cords than the non-COVID group. The median age was younger in the COVID group. COVID pandemic an enormous number of intubations and tracheotomies have been performed. As a result, there will be an increased prevalence of tracheal stenosis. Most of these cases can be effectively treated with surgery. Dealing with complex inoperable cases remains a dilemma. Our case series/research article is an attempt to provide an easy technique with a high cure rate.


Viscoelastic response of the lateral side of the ankle to cyclic inversion: a time course analysis.
Although important, viscoelastic behavior of the ankle's lateral side has rarely been studied. The present study assesses the viscoelastic behavior during cyclic inversions. Eighteen recreationally active healthy males underwent 40 passive cyclic inversions using a Biodex dynamometer at 5 °/s through 80% of maximum range of motion. Energy absorption and restitution and dissipation coefficient were calculated for each repetition. Changes in the mean of the dependent variables for repetitions 1 (R1 ), R5 , R10 , R15 , R20 , R25 , R30 , R35 and R40 were compared by three one-way analyses of variance with repeated measures. There was a significant difference between the means of energy absorption for the selected repetitions from R1 to R20 (P < 0.01), but there was no significant difference between them from R20 to R40 (P > 0.05). There was no significant difference between the means of energy restitution for the selected repetitions (P > 0.05). Whereas there was no significant difference consecutively between the means of dissipative coefficient for the selected repetitions (P > 0.05), there was a significant difference between the means of R30 or R40 relative to the baseline (P < 0.005). The decrease in the energy absorbed and the dissipation coefficient following repeated inversions may be due to the slippage of collagen fibers. The decrease in the shock absorbing ability of the tissues may expose them to injury.


Studies on the epidemiology of bluetongue virus in China.
Sentinel herds of large ruminants were established at five centres in Yunnan Province, Peoples Republic of China, between 1995 and 1997. The application of a sensitive antigen capture ELISA to facilitate virus isolation procedures led to the isolation of 108 strains of bluetongue (BLU) virus. Serotypes isolated included types 1, 2, 3, 4, 9, 11, 12, 15, 16, 21 and 23. Virus transmission occurred over a period of 1-3 months at each of the four positive sites, giving an overall BLU virus transmission period for the province of 5 months, from early June to early November. The greatest level of transmission took place in July and August. The duration of viraemia in individual animals varied from 1 to 7 weeks, with a mean calculated for each serotype between 6 and 20 days. The study represents the first detailed investigation of the epidemiology of BLU in China utilizing sentinel herds.


Synthesis and in vitro evaluation of inhibitors of intestinal cholesterol absorption.
We have utilized our recently developed in vitro assay to address two key questions in the design of small-molecule cholesterol absorption inhibitors using ezetimibe, the only drug yet approved for the inhibition of cholesterol absorption in the small intestine, as a starting point: (1) the role of glycosylation and (2) the importance of the beta-lactam scaffold of ezetimibe for inhibitory activity. A wide range of nonhydrolyzable phenolic glycosides of ezetimibe were synthesized and demonstrated to be active inhibitors of cholesterol absorption using the brush border membrane vesicle assay. The analogous azetidines provided access to a variety of inhibitors in vitro, suggesting that the beta-lactam of ezetimibe merely serves as a ring scaffold to appropriately position the required substituents. Our findings highlight several promising strategies for the design of alternative small-molecule cholesterol absorption inhibitors that could ultimately be useful in preventing cardiovascular disease by lowering blood cholesterol levels.


Interchain impacts on electronic structures of heterocyclic oligomers and polymers containing group 14, 15, and 16 heteroatoms: quantum chemical calculations in combination with molecular dynamics simulations.
The packing structures and packing effects on excitation energies of oligomers of polyfuran (PFu), polypyrrole (PPy), polycyclopentidene (PCp), polythiophene (PTh), polyphosphole (PPh), and polysilole (PSi) are comparatively studied by employing molecular dynamics (MD) simulations and time-dependent density functional theory (TDDFT) calculations. The dependence of packing structures on the main group of heteroatoms in the five-membered heterocyclic oligomers is exhibited from MD simulations. The planarity of backbones and the population of pi-stacked structures increase with the heteroatoms going from group 14 to group 16; i.e., PCp < PPy < PFu; PSi < PPh < PTh. The polymers with the third row elements, PSi and PPh, tend to have larger chain flexibilities in the packing systems than those with the second row elements, PCp and PPy, respectively. On the basis of the second-order Møller-Plesset perturbation (MP2) and natural bond orbital (NBO) calculations of the pi-stacked pairs, the difference in pi-stack orientations, head-to-tail vs head-to-head, between various packing systems is rationalized by individual interchain bond orbital interactions involved with heteroatoms. The packing systems with higher row elements tend to have narrower band gaps. The band gaps are closely related to the chain torsions driven by interchain interactions. The noticeable chain distortions in the packing systems of PCp, PSi, and PPh lead to the significant increase of band gaps in comparison with those appraised from periodic boundary conditions (PBC) calculations on their planar isolated chains.


Recombinant Antibodies in Veterinary Medicine: An Update.
The production of recombinant antibodies has had a tremendous impact on several research fields, most prominently in biotechnology, immunology and medicine, enabling enormous advances in each. Thus far, a broad diversity of recombinant antibody (rAb) forms have been designed and expressed using different expression systems. Even though the majority of rAbs approved for clinical use are targeted to humans, advances in veterinary medicine seem promising. The aim of this mini-review is to present an update regarding the rAbs in veterinary medicine reported to date, as well as their potential use in diagnostics, prophylaxis and therapeutics. Full- and single-chain fragment variables are the most common forms of rAbs developed for the detection, prevention and control of parasitic, bacterial and viral diseases, as well as pain and cancer treatment. Nonetheless, advances in research seem to be skewed toward economically important animals, such as pigs, cows, poultry and dogs. Although significant results have been obtained from the rAbs reported here, most have not been developed enough to be approved. Further research and clinical trials should be encouraged to enable important findings to fulfill their intended potential to improve animal well-being.


Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage.
Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by the expression of BCR-ABL. Loss of p53 has not been implicated as important for the development of CML. Mutations in p53 protein are infrequent, however they correlate with the disease progression. The absence of p53 mutations does not exclude the possibility that other dysfunctions play an important role in CML pathology. Acetylation represents a very potent posttranslational mechanism regulating p53 stability, transcriptional activity and localization. In this study we have investigated whether the expression of BCR-ABL could influence the acetylation of p53, specifically at lysine 317/320 (K317/K320), which has been shown to regulate nuclear export and transcription-independent apoptotic activity of p53. We found that BCR-ABL expression increases K317 acetylation of p53 and is able to prevent a drop in acetylation observed upon DNA damage, followed by translocation of p53 to the cytoplasm and by Bax activation. We have shown that this site plays a crucial role in the regulation of p53 localization and p53-dependent, Bax-mediated apoptosis. Our study presents a novel BCR-ABL-dependent mechanism protecting from DNA-damage-induced cell death. It can, in addition to already known mechanisms, explain the resistance to p53-dependent apoptosis observed in CML cells expressing wt p53. We propose that the acetyltransferases regulating the p53 acetylation could be an interesting and potent target for therapeutic intervention.


Transradial percutaneous coronary intervention in cardiogenic shock: a single-center experience.
Use of the transradial approach (TRA) in percutaneous coronary intervention (PCI) has increased in recent years. TRA has a lower mortality rate than the transfemoral approach (TFA) in patients with acute coronary syndrome. Comparative studies have systematically excluded patients with cardiogenic shock (CS). We performed a prospective, observational registry study of consecutive patients undergoing emergent revascularization between February 2007 and January 2012. An analysis of the clinical evolution of patients with CS during hospitalization was performed. Of 1,400 emergency procedures, 122 had CS, of which 80 underwent PCI by TRA (65.6%) and 42 underwent PCI by TFA (34.3%). The main reason for choosing TFA was the absence of radial pulse (54.9%). Mortality (64.3% vs 32.5%, P = .001), serious access site complications (11.9% vs 2.5%, P = .03), access site complications requiring blood transfusion (7.1% vs 0%, P = .04), and major adverse cardiac events (death, infarction, stroke, serious bleeding, and postanoxic encephalopathy) (73.8% vs 43.8%, P = .001) were greater in patients treated by TFA. In the multivariate analysis, TRA was a predictor of mortality (odds ratio [OR] 0.39 [0.15-0.97]); other predictive factors were age ≥75 years (3.47 [1.35-8.92]), previous treatment with diuretics (3.67 [1.21-11.12]), and success of the procedure (0.07 [0.02-0.24]). Transradial approach for PCI is possible and safe in up to two-thirds of patients with CS. Absence of radial pulse was the main factor preventing use of TRA. In multivariate analysis, TRA was associated with a lower risk of mortality.


Seroprevalence of COVID-19 IgG antibodies among healthcare workers of Pakistan: a cross-sectional study assessing exposure to COVID-19 and identification of high-risk subgroups.
In this study, we aimed to find the seroprevalence of healthcare workers (HCWs) of Pakistan involved in the treatment and care of patients with COVID-19. This was a cross-sectional study and total of 15 000 HCWs involved in providing services and care to the patients with COVID-19 were randomly selected from all over Pakistan. Informed consent was taken from all participants and were included according to inclusion and exclusion criteria. All testing was done on serum samples for the qualitative detection of SARS-CoV-2 IgG antibodies using Abbott Chemiluminescent microparticle immunoassay. An index of 1.4 was used as a cut-off to mark reactive and non-reactive cases. SPSS V.23.0 was used for data analysis. Immune status of the study population depicting seroprevalence among HCWs. Out of all the candidates, majority of the HCWs were men (61.9%) and were doctors (62.4%). The mean age of participants was 32.8 years (SD 8.7) and majority were asymptomatic (51.8%). In this study, 33% of the HCWs were reactive for SARS-CoV-2 IgG antibody. Around 44% of the reactive cases were asymptomatic. The symptoms more significantly associated with seropositivity were: fever (OR 1.31; 95% CI 1.16 to 1.48), headache (OR 2.43; 95% CI 2.16 to 2.73), cough and shortness of breath (OR 2.10; 95% CI 1.91 to 2.31), loss of sense of smell or taste (OR 3.70; 95% CI 3.29 to 4.17) (p<0.001). Factors which showed significant association with the presence of antibodies were professional category (absolute risk (AR) 0.09; OR 1.46; 95% CI 1.36 to 1.56), availability of protective masks (AR 0.02; OR 0.90; 95% CI 0.84 to 0.96), safety goggles (AR 0.02; OR 0.90; 95% CI 0.84 to 0.97) and living arrangements (AR 0.03; OR 1.12; 95% CI 1.04 to 1.20) (p<0.05). Our study showed a high seropositivity of HCWs dealing with patients with COVID-19 in Pakistan revealing significant association with professional category, nature of work place and precautions taken while performing duties.


Mutagenesis by host antimicrobial peptides: insights into microbial evolution during chronic infections.
Antimicrobial peptides (AMPs) are produced by the mammalian immune system to fight invading pathogens. The best understood function of AMPs is to integrate into the membranes of microbes, thereby disrupting and killing cells. However, a recent study [PLoS Pathogens (2014) 10, e1004083] provides evidence that at subinhibitory levels, AMPs promote mutations in bacterial DNA, which enhance bacterial survival. In particular, in the bacterium Pseudomonas aeruginosa, one AMP called LL-37 can promote mutations, which enable the bacteria to overproduce a protective sugar coating, a process called mucoid conversion. P. aeruginosa mucoid conversion is a major risk factor for those suffering from cystic fibrosis (CF), one of the most common lethal, heritable diseases in the US. LL-37 was found to produce mutations by penetrating the bacterial cell and binding to bacterial DNA. It was proposed that LL-37 binding DNA disrupts normal DNA replication and potentiates mutations. Importantly, LL-37 induced mutagenesis was also found to promote resistance to rifampicin in both P. aeruginosa and E. coli. This suggests that AMP-induced mutagenesis may be important for a broad range of chronic diseases and pathogens.


Approaches to measure paediatric chemotherapy-induced peripheral neurotoxicity: a systematic review.
In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the published literature concerning the evaluation of assessment measures for paediatric chemotherapy-induced peripheral neurotoxicity. We searched PubMed, CINAHL, PsycINFO, and Embase on Nov 7-8, 2018; of 1409 articles, seven met the inclusion criteria. A total of 335 children (excluding ten healthy controls) were enrolled in the seven studies and the sample sizes ranged from 17 to 86 individuals. 276 (82%) of the 335 children were actively undergoing chemotherapy treatment. Most studies did not comprehensively evaluate the psychometric properties of assessment measures for chemotherapy-induced peripheral neurotoxicity. By use of a narrative analysis that combined approaches from the Joanna Briggs Institute (Adelaide, SA, Australia) and the quality of diagnostic accuracy studies assessment method (known as QUADAS), only one study was deemed high quality. We identified two variants of the Total Neuropathy Score, two grading scales, two semi-objective tests, one patient-reported outcome, and several mobility measures. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Balis grading scales showed lower sensitivity and specificity than the items of the Total Neuropathy Score. Although there is insufficient evidence to support the use of most approaches to assess chemotherapy-induced peripheral neurotoxicity in children, two variants of the Total Neuropathy Score, the pediatric-modified Total Neuropathy Score and the Total Neuropathy Score-pediatric vincristine, are promising but require further testing. Other approaches are less sensitive or less feasible. A patient-reported outcome measure for chemotherapy-induced peripheral neurotoxicity in children is needed.


Comparison of DSM-IV symptoms in elementary school-age children with PDD versus clinic and community samples.
This study compares DSM-IV symptoms in children (ages 6 to 12 years) with pervasive developmental disorder (PDD), clinic controls, and community-based samples. Parents/teachers completed the Child Symptom Inventory-4 for four samples: PDD (N = 284/284) and non-PDD psychiatric clinic referrals (N = 189/181) and pupils in regular (N = 385/404) and special (N = 61/60) education classes. The PDD group received higher symptom severity ratings than the regular education group, but was similar to the non-PDD clinic sample. Screening prevalence rates were highest for ADHD, ODD, and generalized anxiety disorder. PDD subtypes exhibited differentially higher rates of psychiatric symptoms. The magnitude of rater and gender differences in symptom severity ratings was modest. Clinic-referred children with PDD exhibit a pattern of psychiatric symptoms highly similar to nonPDD clinic referrals. Although much additional research is needed on comorbidity, these symptoms have important treatment implications.


Progress in Brewing Science and Beer Production.
The brewing of beer is an ancient biotechnology, the unit processes of which have not changed in hundreds of years. Equally, scientific study within the brewing industry not only has ensured that modern beer making is highly controlled, leading to highly consistent, high-quality, healthful beverages, but also has informed many other fermentation-based industries.


Structural and Functional Characterization of PR-4 SUGARWINs From Sugarcaneand Their Role in Plant Defense.
SUGARWIN1 and 2 are defense proteins from sugarcane. Their gene expression is known to be induced in response to wound and Diatraea saccharalis damage. Although the recombinant SUGARWIN protein does not affect insect development, it promotes significant morphological and physiological changes in Fusarium verticillioides and Colletotrichum falcatum, which lead to fungal cell death via apoptosis. In this study, we deepen our understanding of the role of SUGARWINs in plant defense and the molecular mechanisms by which these proteins affect fungi by elucidating their molecular targets. Our results show that SUGARWINs play an important role in plant defense against opportunistic pathogens. We demonstrated that SUGARWINs are induced by C. falcatum, and the induction of SUGARWINs can vary among sugarcane varieties. The sugarcane variety exhibiting the highest level of SUGARWIN induction exhibited a considerable reduction in C. falcatum infection. Furthermore, SUGARWIN1 exhibited ribonuclease, chitosanase, and chitinase activity, whereas SUGARWIN2 exhibited only chitosanase activity. This variable enzymatic specificity seems to be the result of divergent amino acid composition within the substrate-binding site.


Isolation and Antibiotic Screening of Fungi from a Hydrothermal Vent Site and Characterization of Secondary Metabolites from a Penicillium Isolate.
Five new compounds were isolated from Penicillium sp. Y-5-2 including an austin derivative 4, four isocoumarins 9, 11, 12, and 13, together with two known isocoumarins 8 and 10, and six known austin derivatives 1, 2, 3, 5, 6, and 7 and one phenol 14. Their structures and relative configurations were established by spectroscopic means. The absolute configurations of 4, 11, and 13 were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. The cyclization of the pentan-2-ol pendant at C-3 in compound 13 allowed the assignment of a new 2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromene isocoumarin skeleton. New compounds 9, 11, and 13 revealed inhibitory activities against E. coli at MIC values around 32 μg/mL. The known compound 14 showed potent antibiotic activity against Staphylococcus aureus and Bacillus subtilis with MIC values 8 and 2 μg/mL, respectively, with no cytotoxicity when tested in vitro. A rapid and efficient technique for selecting antibiotic fungal strain among eight marine-derived fungi was also described.


Differentiation and enrichment of hepatocyte-like cells from human embryonic stem cells in vitro and in vivo.
Human embryonic stem cells (hESC) may provide a cell source for functional hepatocytes. The aim of this study is to establish a viable human hepatocyte-like cell line from hESC that can be used for cell-based therapies. The differentiated hESC were enriched by transducing with a lentivirus vector containing the green fluorescent protein (GFP) gene driven by the alpha1-antitrypsin promoter; the GFP gene is expressed in committed hepatocyte progenitors and hepatocytes. GFP+ hESC were purified by laser microdissection and pressure catapulting. In addition, differentiated hESC that were transduced with a lentivirus triple-fusion vector were transplanted into NOD-SCID mice, and the luciferase-induced bioluminescence in the livers was evaluated by a charge-coupled device camera. GFP+ hESC expressed a large series of liver-specific genes, and expression levels of these genes were significantly improved by purifying GFP+ hESC; our results demonstrated that purified differentiated hESC express nearly physiological levels of liver-specific genes and have liver-specific functions that are comparable to those of primary human hepatocytes. The differentiated hESC survived and engrafted in mouse livers, and human liver-specific mRNA and protein species were detected in the transplanted mouse liver and serum at 3 weeks after transplantation. This is the first time that human albumin generated by hESC-derived hepatocytes was detected in the serum of an animal model. This also represents the first successful transplantation of differentiated hESC in an animal liver and the first bioluminescence imaging of hESC in the liver. This study is an initial step in establishing a viable hepatocyte-like cell line from hESC. Disclosure of potential conflicts of interest is found at the end of this article.


Effects of frontalis tension level on discrimination task accuracy and reaction time.
The frontalis muscle is a focal point of many relaxation training programmes, so the effects of varying frontalis tension levels on concurrent task performance need consideration when recommending in situ muscle relaxation. Two experiments are reported; performance on a discrimination task was examined across high, moderate, and low induced frontalis tension. When length of exposure to the task stimuli was unlimited, accuracy of discrimination was affected by tension; when exposure was limited, reaction time was affected. In both experiments the high frontalis tension resulted in better performance than the other levels. Implications for the practice of in situ relaxation are considered.


Expansion of human lymphocyte populations expressing specific immune reactivities. II. A comparison of immune reactivities in human T lymphocyte lines derived from allogeneically primed cultures and maintained with lectins or conditioned medium.
In a previous paper, lectins were shown to allow a strong expansion of in vitro primed cells; among the lectins tested, PKW but not PHA (nor Con A) was found to reactivate CTLs. We then asked two further questions: Could one maintain a long term expansion of human T cells using iterative lectin stimulation? And, if so, could the immune reactivities, once expressed in the original primed cells, also be maintained? We report here that lectins remain potent mitogens for primed cells, and allow good expansion over many cycles, provided fresh irradiated cells (autologous or not to the responder) are added to the cultures. When PKW is used as the iterative mitogen, both the specific proliferation (PLT) and the specific cytotoxicity are maintained after each cycle. When PHA is the iterative stimulant, only the specific proliferation (PLT) is maintained, while no measurable cytolysis is present. However, if iteratively PHA stimulated primed cells are now cultured in the absence of PHA, even without additional specific stimulation, cytolytic activity is recovered from the cultures. In parallel, primed cells iteratively expanded using conditioned medium appear to retain both their specific lytic function and their specific proliferative function. Preliminary data suggest that the cloning efficiency when using lectins is higher than when using conditioned medium.


An innovative "unlocked mechanism" by a double key avenue for one-pot detection of microRNA-21 and microRNA-141.
The accurate and quantitative detection of microRNAs (miRNAs) as next-generation, reliable biomarkers will provide vital information for cancer research and treatment. However, their unique, intrinsic features pose quite a challenge for miRNA profiling, especially for multiplexed detection. Thus, there is a strong and an ever-growing need to develop an accurate, simple, sensitive and specific miRNA sensing method. Methods: In this study, a simple and novel sensor is presented that uses a flow cytometry (FCM) method based on the double key "unlocked mechanism" and a fluorescence enrichment signal amplification strategy. The "unlocked mechanism" was cleverly designed via using hairpin DNA probes (HDs) labeled by fluorescent particles (FS) as the lock to block part of them, which can specifically hybridize with the probe on polystyrene microparticles (PS). The target miRNA and duplex-specific nuclease (DSN) forming the double key can specifically open the HDs and cleave a single-stranded DNA (ssDNA) into DNA/RNA dimers circularly in order to unlock the special part of the HDs to be specially enriched further on the PS. Results: The designed sensor with a hairpin structure and DSN special performance was found to have a high specificity. The circularly unlocking fluorescent probes and fluorescent signal enrichment can be beneficial for achieving a high sensitivity with a detection limit of 3.39 fM for miRNA-21. Meanwhile, the performance of multiplexing was estimated by simultaneous detection of miR-21 and miR-141, and the method also allowed for miR-21 detection in breast cancer blood samples. Conclusion: The designed sensor based on an "unlocked mechanism" and a signal enrichment strategy resulted in a one-pot, highly specific and sensitive detection of multiplex miRNAs. The whole detection without the need for a complex purification process is based on a FCM and is expected to have a great value in cancer diagnosis and biomedical research.


Key to the currently recognized species of Limnias Schrank, 1803 (Rotifera, Monogononta, Gnesiotrocha, Flosculariidae).
Although the most widely used key to the Rotifera subsumes six species of the sessile genus Limnias within two species groups (L. ceratophylli and L. melicerta), the original descriptions of these forms are sufficiently different to recognize them as distinct entities. We used these descriptions and all available literature on these species to develop dichotomous and formula keys to the six species based on easily recognizable morphological characters. As part of our review we added relevant ecological information from published sources, as well as our own data. We also discuss the need for additional observations of morphological, behavioral, life history, and genetic features to better understand the diversity of this widespread genus.


Alcohol-induced delay of viability loss in stationary-phase cultures of Escherichia coli.
During prolonged incubation in stationary phase Escherichia coli undergoes starvation-induced differentiation, resulting in highly resistant cells. In rich medium with high amino acid content further incubation of cultures at high cell density leads to the generation of a population of cells no longer able to form colonies. The viability loss is due to some component of spent medium, active at high pH and high cell density, and can be prevented either by keeping the pH close to neutrality, by washing off the nonsalt components of the medium, or by keeping the saturating cell density low. Exposure to short-chain n-alcohols within a specific time window in stationary phase also prevents viability loss, in an rpoS-dependent fashion. The development of stress resistance, a hallmark of stationary-phase cells, is affected following alcohol treatment, as is the response to extracellular factors in spent medium. Alcohols seem to block cells in an early phase of starvation-induced differentiation, most likely by interfering with processes important for regulation of sigma(s) such as cell density signals and sensing the nutrient content of the medium.


[Evaluation of the surgical treatment of trapeziometacarpal arthroses].
The authors describe their experience, from July 1995 to December 1996, in the management of patients suffering from trapeziometacarpal degenerative arthrosis. Dell's classification is used for disease staging. The results of two different techniques are compared: 1) distal tenotomy of supranumerary insertions of abductor pollicis longus; and 2) trapeziectomy with tendon interposition arthroplasty and ligamentoplasty using the flexor carpi radialis.


Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa.
In this work, we studied the proband in a small nuclear family of Chinese and Dutch/German descent and identified two novel mutations in the type VII collagen gene leading to recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens variant (HS-RDEB). The maternal mutation is a single base pair deletion of a cytosine nucleotide in exon 26, designated 3472delC, resulting in a frameshift and a premature termination codon (PTC) within the same exon, 7 bp downstream of the site of the mutation. The paternal mutation is a G-->A transition located at the 5' donor splice site within intron 51, designated IVS51 + 1G-->A. This mutation leads to the activation of a cryptic splice site, 32 bp downstream of the mutation site and to subsequent aberrant out-of-frame splicing, resulting in two alternative mRNA transcripts and a downstream PTC. To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family.


Intentionality in adherence to long-term therapies. Results from an online survey of 3,001 patients with cardio-metabolic pathologies in France.
Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence. This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor's attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients' adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire. Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, "I take my medication because I am used to taking it." This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as "unintentional adherence." 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study. We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians' attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula.


A plastic surgery office-based Website: an asset to any practice!
We are living in a "connected world" and our patients are taking a more active role in their health care management as well as educating themselves about health-related issues. An office-based website can be an effective tool for plastic surgery practices as well as plastic and reconstructive surgical nurses. This type of a website can serve as a source of information for potential and current clients.


Null effect of anodal and cathodal transcranial direct current stimulation (tDCS) on own- and other-race face recognition.
Successful face recognition is important for social interactions and public security. Although some preliminary evidence suggests that anodal and cathodal transcranial direct current stimulation (tDCS) might modulate own- and other-race face identification, respectively, the findings are largely inconsistent. Hence, we examined the effect of both anodal and cathodal tDCS on the recognition of own- and other-race faces. Ninety participants first completed own- and other-race Cambridge Face Memory Test (CFMT) as baseline measurements. Next, they received either anodal tDCS, cathodal tDCS or sham stimulation and finally they completed alternative versions of the own- and other-race CFMT. No difference in performance, in terms of accuracy and reaction time, for own- and other-race face recognition between anodal tDCS, cathodal tDCS and sham stimulation was found. Our findings cast doubt upon the efficacy of tDCS to modulate performance in face identification tasks.


Sixth Nerve Palsy from Cholesterol Granuloma of the Petrous Apex.
Herein, we report a patient who had an isolated sixth nerve palsy due to a petrous apex cholesterol granuloma. The sixth nerve palsy appeared acutely and then spontaneously resolved over several months, initially suggesting a microvascular origin of the palsy. Subsequent recurrences of the palsy indicated a different pathophysiologic etiology and MRI revealed the lesion at the petrous apex. Surgical resection improved the compressive effect of the lesion at Dorello's canal and clinical improvement was observed. A relapsing-remitting sixth nerve palsy is an unusual presentation of this rare lesion.


[Four cases of extrapyramidal effects following the treatment of hyperemesis gravidarum with triflupromazin (author's transl)].
Report of four cases of extrapyramidal effects following the treatment of hyperemesis gravidarum with neuroleptica (Triflupromazin). A short list is made of the common preparations and their neuroleptic potency. The pathophysiological theory is mentioned and the simple and very effectfull therapy with anti-parkinsonism-drugs.


Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in Candida albicans.
Fatty acids have known antifungal effects and are used in over-the-counter topical treatments. Screening of a collection of gene knockouts in Candida albicans revealed that one strain, carrying a deletion of the transcription factor DAL81, is very susceptible to the medium-chain fatty acid undecanoic acid. However, reintroducing DAL81 does not restore resistance, and editing DAL81 in a different background does not introduce sensitivity. Whole-genome sequencing revealed that the C. albicansdal81Δ/Δ strain has an extra copy of chromosomes 5 and 7. Reversion to resistance to undecanoic acid was induced by growing the sensitive strain in yeast extract-peptone-dextrose with 60 μg/ml undecanoic acid for up to 9 days. Nine isolates that regained some resistance to undecanoic acid lost one copy of chromosome 7. The copy number of chromosome 5 does not appear to affect resistance to fatty acids. Moreover, the sensitivity may be related to having two copies of haplotype B of chromosome 7. In addition, we find that C. albicans strain SN152, used to delete DAL81 and many other genes, has undergone a major loss of heterozygosity event on chromosome 2 and a smaller one on chromosome 3.IMPORTANCE Aneuploidy (changes in chromosome number) and loss of heterozygosity (LOH) occur frequently in the human-pathogenic yeast Candida albicans and are associated with adaptation to stress and to antifungal drugs. Aneuploidy and LOH can also be induced during laboratory manipulations, such as during genetic transformation. We find that C. albicans strain SN152, commonly used to generate gene deletions, has undergone a major LOH event on chromosome 2. One deletion strain generated in this background has acquired extra copies of chromosomes 5 and 7. We find that trisomy (three copies) of chromosome 7 is associated with sensitivity to fatty acids.


Pseudoaneurysm formation at the rupture site of a middle cerebral artery aneurysm--case report.
A 42-year-old man suffered subarachnoid hemorrhage manifesting as sudden severe headache one month before admission. On admission, his headache had subsided and he had no neurological deficits. Cerebral angiography demonstrated an aneurysm originating from the bifurcation of the right middle cerebral artery. The aneurysm was irregular, with a snowman-like shape. Neck clipping of the aneurysm was carried out through a right pterional approach. Intraoperatively, a red, pulsating sac mimicking a blood clot (the snowman's "head") was located over the yellowish, thick-walled portion of the aneurysm. Exploration around the aneurysm detached the red sac from the thick-walled portion of the aneurysm. There was a small tear in the apex of the thick-walled aneurysm sac. A Sugita clip was applied to the neck of the true aneurysm. The postoperative course was uneventful and he was discharged one month later without neurological deficits. Histological examination of the red-colored sac showed the features of pseudoaneurysm. The red sac may have been a pseudoaneurysm covering the rupture site of the true aneurysm.


Not now but later - a qualitative study of non-exercising pregnant women's views and experiences of exercise.
Evidence has shown that there are several physical and mental advantages of exercise during pregnancy. Despite this, the recommendations for exercise during pregnancy are poorly fulfilled. The aim of this study was to illuminate non-exercising pregnant women's views and experiences concerning exercise before and during pregnancy. The study had a qualitative design with an inductive approach and was analysed by content analysis. A total of 16 individual and face-to-face interviews were conducted with healthy pregnant women, mainly in the third trimester and living in Sweden. The participating women had not been exercising 3 months before pregnancy or during pregnancy. The main category "Insurmountable now, but possible in the future" was based on the four categories: "Lost and lack of routines", "Feelings of inadequacy", "Having a different focus" and "Need for support". The women experienced that their lack of routines was a major barrier that prevented them from exercising. Other factors that contributed were, for example, pregnancy-related problems, long working days and prioritizing family life. The women described it as difficult to combine exercise with their focus on the pregnancy and they missed continuous support from the antenatal care provider. The women expressed a need for suggestions concerning exercise during pregnancy and follow-up on previous counselling, especially when pregnancy-related issues arose. Information about easily accessible alternatives or simple home exercises was requested. They felt immobile and were not satisfied with their inactivity and tried to partly compensate with everyday activities. The women identified the postpartum period as an important possibility for becoming more active, for their own sake, but also because they wanted to become role models for their children. Continuous support during pregnancy is needed concerning exercise. Pregnancy is mostly a barrier that prevents exercise for this group of women but, at the same time, may be a motivator and a possibility for better health. As the result showed that these women were highly motivated to a life-style change post-pregnancy, it may be crucial to support previously non-exercising women postpartum.