Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals.
Paeoniflorin is the major active compound of total glycoside of paeony in Paeonia lactiflora Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in Caenorhabditis elegans induced by Pseudomonas aeruginosa infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of P. aeruginosa infected nematodes at the immunosuppression stage could be significantly increased by 25-100 mg/L paeoniflorin treatment. P. aeruginosa accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of bar-1, pmk-1, and egl-1 required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of bar-1, pmk-1, and egl-1 inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the P. aeruginosa accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.


Fetal liver magnetic resonance imaging in anterior body wall defects: a study of specimens from the museum of pathology.
The purpose of the study was to evaluate the appearance of liver anatomy in fetuses with complex anterior body wall defects (ABWD) using magnetic resonance imaging (MRI). Nineteen specimens from the National Museum of Pathological Anatomy (Vienna) with a wide range of ABWD were studied on a 1.5-T MR scanner (T1- and T2-weighted sequences) with special focus on the liver and the relationship between the large lesion and the adjacent structures. The contrast of T2-weighted sequences was superior to that of the T1-weighted images. The liver was found in an intraabdominal location in 3 cases and in a completely extraabdominal location in 11 fetuses. Five fetuses had a very special configuration or position of the liver. Furthermore, the images showed an anteriorly located confluence of hepatic veins into the inferior vena cava in 5 specimens. Associated malformations of the complexly structured malformations involved the urogenital tract, the central nervous system (CNS), the cardiac system and the musculoskeletal system. Prenatal fast magnetic resonance imaging (MRI) in one fetus confirmed the liver in a both inside/outside position, whereas the diagnosis at fetal ultrasound scan (US) in this case had been uncertain. These results show that MRI may play an important part in antenatal diagnosis of ABWD, complementary to prenatal US. Prenatal fast MRI should be considered if fetal US yields ambiguous findings.


Modified DMEM xenic culture medium for propagation, isolation and maintenance of Balantioides coli.
Balantioides coli is a known ciliated zoonotic protozoan that mainly causes diarrhea in humans and pigs. An efficient and reliable culture system for this parasite remains unavailable until now. In this study, a modified Dulbecco's modified eagle medium (DMEM) with pH 7.0-7.5, containing 5 mg/mL starch and 20% new calf serum, was optimized for propagation of B. coli at 28°C-32°C. At the growth-peaking stage, the average trophozoite density was up to 12,970 trophozoites per milliliter. A reproducible protocol for isolation and maintenance of this parasite was also developed based on the modified DMEM culture medium. Moreover, cloning results of B. colipopulations showed that 250 trophozoites in 3 mL modified DMEM medium were the minimal number of trophozoites that propagated to the growth-peaking stage, and finally obtained the individual population. However, less than 250 trophozoites failed to continuously grow in the modified DMEM culture medium under the optimal conditions for growth of B. coli. These data showed that the modified DMEM culture medium is an ideal and efficient medium for propagation and maintenance of B. coli in vitro and will help studies on its biology, genome, transcriptome, proteome, and drug screening.


The strategic significance of helping a billion children learn about health.
"The children should and can play a decisive role in the Health for All movement. And reaching them now should be given its rightful place and significance in the overall HFA strategy in every country, in every region, and in the global plan of action".


Radiographic patterns on Chest X-ray as a supporting imaging tool in triaging of suspected Corona Virus Disease (COVID) patients.
To evaluate the radiographic patterns on Chest X-Ray (CXR) in accordance with Modified Brixia Scoring as supporting imaging tool in triaging of Corona Virus Disease (COVID-19) pneumonia. In this cross-sectional study, chest radiographs of suspected COVID patients at emergency triage, Lady Reading Hospital (LRH) from April 18th to July 22nd 2020 were evaluated for patterns of COVID pneumonia and scored in accordance with modified Brixia score. Each zone was categorized as score of "one" for interstitial pattern, "two" for mixed interstitial /alveolar pattern and "three" for alveolar pattern. Radiographic patterns consistent with COVID pneumonia or patients having strong clinical suspicion were advised Polymerase Chain Reaction (PCR) tests. Total of 2,225 individuals were screened for patterns of COVID-19 pneumonia on chest radiograph. Out of these 1465(65.8%) had normal chest radiograph and 760(34.2%) had abnormal findings. Out of the total, 648 suspected COVID patients were selected for PCR. The radiographic patterns ranged from mixed interstitial/alveolar pattern in 261(40.3%) patients, alveolar pattern in 231(35.6%), interstitial pattern in 87(13.4%), pleural effusion in 12(1.9%), other findings in 5(0.8%) while 52(8%) suspected Covid patients had normal radiographs. The PCR was positive in 326(50.3%), negative in 100(15.4%) and inconclusive in 60(9.3%) while 162(25%) were lost to follow up. Amongst the 52 suspected Covid patients having normal chest radiographs, 10 were positive on PCR, 21 negative, seven suspected and two inconclusive, while 12 were lost to follow up. Chest radiograph is used for triaging of suspected COVID pneumonia patients in emergency settings. It assesses the severity of disease according to modified Brixia scoring for treatment plan.


A comparative study of the toxicity of mercury dichloride and methylmercury, assayed by the Frog Embryo Teratogenesis Assay--Xenopus (FETAX).
The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a powerful and flexible bioassay that makes use of the embryos of the anuran amphibian Xenopus laevis. The FETAX can detect xenobiotics that affect embryonic development, when mortality, teratogenicity and growth inhibition are used as endpoints. The FETAX was used to compare the embryotoxic and teratogenic potentials of two chemical species of mercury, inorganic mercury(II) chloride (HgCl2) and organic methylmercury chloride (MeHgCl). A higher toxicity of MeHgCl (the estimated median lethal concentration [LC50] and median teratogenic concentration [TC50] were 0.313microM and 0.236microM, respectively) over HgCl2, with estimated LC50 and TC50 values of 0.601microM and 0.513microM, respectively). On the basis of these results, HgCl2 and MeHgCl can be classified as "slightly teratogenic compounds", as the ratio of LC50/TC50 is less than 1.5. There was a significant deviation from the commonly described monotonic behaviour of the concentration-response curves, suggesting a hormetic effect of both species of mercury. Uptake experiments, followed by neutron activation analysis, showed a higher incorporation of mercury in embryos exposed to MeHgCl compared with those exposed to HgCl2. Interestingly, Hg- exposed embryos showed a higher content of selenium and zinc than did control embryos.


Use of PC12 cells and rat superior cervical ganglion sympathetic neurons as models for neuroprotective assays relevant to Parkinson's disease.
Cellular models composed of primary neuronal cultures or neuron-like cell lines are commonly used to study neuron cell death and to test the neuroprotective properties of specific compounds. Cellular models are easily accessible, permitting dissection and modulation of signaling pathways involved in neuron death. For example, drug or shRNA delivery is more straightforward since there is no blood-brain barrier to cross. However, since these models have their limitations, any important findings should ultimately be verified with animal models and human samples. Here, we describe two cellular models that can be used as a highly informative and easy to use starting point for testing potential neuroprotective drugs for Parkinson's disease: PC12 cells and sympathetic neuronal cell cultures. We describe in detail the protocols needed to apply these models to study neuroprotection in the context of Parkinson's disease.


Scintigraphic study of regenerative nodules due to fulminant hepatic failure.
We report the case of a 25-year-old woman with fulminant hepatic failure (FHF). Liver scintigraphy using (99m)Tc-galactosyl human serum albumin (GSA) and (99m)Tc-phytate produced interesting findings; regenerative nodules appeared as nodules of increased accumulation of (99m)Tc-GSA, whereas these nodules were expressed as defects of accumulation of (99m)Tc-phytate. These scintigraphic findings suggested that the functions of hepatocytes in regenerative nodules were maintained, whereas those of Kupffer cells were impaired. Although (99m)Tc-GSA scintigraphy indicated hepatic functional reserve enough to survive, she died despite intensive therapy including plasma exchange. Based on this case, it is recommended that not only (99m)Tc-GSA scintigraphy but also (99m)Tc-phytate scintigraphy is required to evaluate the prognosis of patients with FHF.


A phase II trial of peplomycin in squamous cell carcinoma of the lung.
A phase II trial has been performed in squamous cell carcinoma of the lung using peplomycin. This compound is a bleomycin analogue with less pulmonary toxicity and a broader antitumor effect than bleomycin in experimental animal systems. Twenty-one evaluable patients were treated using a dose schedule of 5 mg/m2 twice weekly intravenously. None of the patients had previously received radiation or chemotherapy. The median dose of peplomycin received was 160 mg (range 45-254). One patient obtained a partial remission lasting 3 months. One out of 21 patients developed clinical symptoms and a decrease in the lung function test performed during treatment indicative of toxicity. Other manifestations of toxicity are comparable to those of bleomycin.


Developing catalytic applications of cooperative bimetallics: competitive hydroamination/trimerization reactions of isocyanates catalysed by sodium magnesiates.
Mixed-metal reagents [NaMg(CH2SiMe3)3] (1) and [(THF)NaMg(NPh2)3(THF)] [3-(THF)(2)] can act as precatalysts to selectively promote the hydroamination/trimerization of isocyanates (RNCO) depending on the steric bulk of the R substituent.


Responses of the rat superior cervical ganglion in vitro to isoprenaline and bethanechol.
The effects of isoprenaline were studied in isolated rat superior cervical ganglia. Intracellularly recorded excitatory postsynaptic potentials were depressed by isoprenaline in concentrations of 10(-5) to 10(-4)M. In 13 out of 17 cells, isoprenaline caused ganglionic hyperpolarization (mean, 4mV). Changes in the amplitude and contour of antidromic action potentials caused by isoprenaline could be accounted for by the increased membrane potential. A slight increase in membrane input resistance from 44--50.2 megohms (mean values) occurred in about half of the cells. Activation of an ion pump by isoprenaline was suggested by the finding that the hyperpolarization did not occur when the bathing solution contained ouabain (10(-5)M) or lacked Na+ or K+. Characterization of the isoprenaline effects by the use of alpha and beta adrenergic blocking drugs was not possible because of the direct depressant effects of the antagonists. The muscarinic agonist bethanechol (2.5 X 10(-5) to 2.5 X 10(-4)M) caused ganglionic depolarization and increased input membrane resistance (42--52 megohms) during depolarization in each of the cells tested. The ganglionic responses to bethanechol were prevented by atropine.


Effect of chemotherapy on T-lymphocyte subsets in B-cell proliferative disorders.
The T-cell subset distribution and the activity markers of 41 patients with multiple Myeloma, Waldenström's macroglobulinaemia and benign monoclonal gammopathy were repeatedly analysed using monoclonal antibodies (T3, T4, T8, anti-TAC, anti DR) and rosetting techniques. In myeloma and macroglobulinaemia the relative and absolute numbers of T4+ cells were diminished while the absolute number of T8+ cells was not decreased. No significant difference between stage I and III of the myeloma disease was seen. The diminished number of T4+ cells in myeloma was partly due to the effect of chemotherapy. Chemotherapy-induced lymphopenia resulted in a drop of circulating T4+ cells and an inverted T4/T8 cell ratio. Untreated patients with myeloma were not significantly different from patients with benign gammopathy. Patients with macroglobulinaemia differed from patients with myeloma as they had an increased absolute T8 cell count and a significantly elevated percentage of TAC+ (= IL 2 receptor expressing) cells. In macroglobulinaemia chemotherapy affected also the T8+ cell subset. Thus, patients with macroglobulinaemia, but not with myeloma appear to have activated T8+ cells in their circulation.


Arthroscopic treatment for anterior impingement exostosis of the ankle: application of three-dimensional computed tomography.
The purpose of this study was to evaluate the operative results of excision of anterior impingement exostoses of the ankle. Preoperative three-dimensional computed tomography (3DCT) was used to make the diagnoses. The authors evaluated 16 ankles of 16 patients who underwent arthroscopic resection of the osteophytes of their anterior distal tibia or dorsal talus. They were followed up for 24-51 months. All 16 patients had 3DCT preoperatively, which allowed the authors to determine the exact location, shape, size, and number of the osteophytes. All of the osteophytes were resected using arthroscopic techniques. At the time of the most recent follow-up, the mean AOFAS score was 80.5 +/- 4.9 points at preoperation, and 97.0 +/- 3.7 points at the most recent follow-up. There were significant differences between the pre- and postoperative AOFAS scores and those of the most recent follow-up period for each group (p <.0001). It is necessary to clarify the location, size, shape, and number of all of the osteophytes preoperatively using 3DCT, and to then resect them all.


NKG2D triggers cytotoxicity in murine epidermal γδ T cells via PI3K-dependent, Syk/ZAP70-independent signaling pathway.
Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), survey tissue stress through the invariant T-cell receptor (TCR) and non-clonotypic receptors such as NKG2D. NKG2D signaling via the DAP10-phosphatidylinositol 3-kinase (PI3K) pathway directly stimulates cytotoxicity in natural killer (NK) cells and costimulates CD8(+) T cells to augment TCR signals. In activated murine NK cells, NKG2D signals also via the DAP12-Syk/ZAP70 pathway that triggers both cytotoxicity and cytokine production. It remains controversial whether NKG2D on DETCs is a primary activating receptor or functions only as a costimulatory receptor, and signaling pathways initiated by NKG2D ligation in DETCs have not been analyzed. We show that stimulation of short-term DETC lines with recombinant NKG2D ligands triggers degranulation (exocytosis of cytotoxic granules) via the PI3K-dependent signaling pathway, but does not induce cytokine production or Syk/ZAP70 activation. Coengagement of TCR or Syk/ZAP70 signaling was not crucial for DETC-mediated killing of NKG2D ligand-expressing target cells. Thus, NKG2D can function as a coactivating stress receptor that directly triggers cytotoxicity in DETCs, at least after priming, via the PI3K-dependent, Syk/ZAP70-independent signaling pathway.


Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.
Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine proteases whereas the carboxylic acids are specific. Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compatible with activated carbonyl functionalities.


The impact of reoperative surgery on aortic root replacement in the United States.
Reoperative sternotomy is associated with poor outcomes after cardiac surgery. We aimed to investigate the impact of reoperative sternotomy on the outcomes after aortic root replacement. All patients who underwent aortic root replacement from January 2011 to June 2020 were identified using the Society of Thoracic Surgeons Adult Cardiac Surgery Database. We compared outcomes between patients who underwent first-time aortic root replacement with those with a history of sternotomy undergoing reoperative sternotomy aortic root replacement using propensity score matching. Subgroup analysis was performed among the reoperative sternotomy aortic root replacement group. A total of 56,447 patients underwent aortic root replacement. Among them, 14,935 (26.5%) underwent reoperative sternotomy aortic root replacement. The annual incidence of reoperative sternotomy aortic root replacement increased from 542 in 2011 to 2300 in 2019. Aneurysm and dissection were more frequently observed in the first-time aortic root replacement group, whereas infective endocarditis was more common in the reoperative sternotomy aortic root replacement group. Propensity score matching yielded 9568 pairs in each group. Cardiopulmonary bypass time was longer in the reoperative sternotomy aortic root replacement group (215 vs 179 minutes, standardized mean difference = 0.43). Operative mortality was higher in the reoperative sternotomy aortic root replacement group (10.8% vs 6.2%, standardized mean difference = 0.17). In the subgroup analysis, logistic regression demonstrated that individual patient repetition of (second or more resternotomy) surgery and annual institutional volume of aortic root replacement were independently associated with operative mortality. The incidence of reoperative sternotomy aortic root replacement might have increased over time. Reoperative sternotomy is a significant risk factor for morbidity and mortality in aortic root replacement. Referral to high-volume aortic centers should be considered in patients undergoing reoperative sternotomy aortic root replacement.


A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.
Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.


Discovery of potent and selective adamantane-based small-molecule P2X(7) receptor antagonists/interleukin-1beta inhibitors.
A novel series of antagonists of the human P2X7 receptor is described. Modification of substituents enabled identification of compounds selective for the rat P2X7 receptor and provides useful pharmacological tools for evaluation of the role of P2X7 in disease.


The effect of nonpharmacological interventions applied by nurses to intensive care patients on the duration of delirium: a meta-analysis study.
It was aimed to determine the effect level of nonpharmacological methods applied by nurses to patients hospitalized in the intensive care unit on the duration of delirium. For this study, relevant studies were accessed by searching in July-October 2022. After the necessary exclusions were made, 14 studies were included in the study. The total sample size of the studies was 1123. According to the results, nonpharmacological interventions applied by nurses to intensive care patients were found to reduce the duration of delirium (SMD: - 0.625, 95% CI: - 1.1040-0.210; Z = - 2.950, p = 0.003, I2 = 93.119%). The country of the study (SMD: - 0.047, p = 0.001) and the types of nonpharmacological interventions used (SMD: - 0.062, p = 0.000) influenced the effect size of modulators on the duration of delirium in ICU patients. Nonpharmacological interventions applied by nurses, who have significant responsibilities in the protection and promotion of health, were found to reduce the duration of delirium in intensive care patients. This study shows that nurses, one of the main components of the multidisciplinary team in intensive care, are successful when they apply nonpharmacological interventions well.


Cancer Immunotherapy Using CAR-T Cells: From the Research Bench to the Assembly Line.
The focus of cancer treatment has recently shifted toward targeted therapies, including immunotherapy, which allow better individualization of care and are hoped to increase the probability of success for patients. Specifically, T cells genetically modified to express chimeric antigen receptors (CARs; CAR-T cells) have generated exciting results. Recent clinical successes with this cutting-edge therapy have helped to push CAR-T cells toward approval for wider use. However, several limitations need to be addressed before the widespread use of CAR-T cells as a standard treatment. Here, a succinct background on adoptive T-cell therapy (ATCT)is given. A brief overview of the structure of CARs, how they are introduced into T cells, and how CAR-T cell expansion and selection is achieved in vitro is then presented. Some of the challenges in CAR design are discussed, as well as the difficulties that arise in large-scale CAR-T cell manufacture that will need to be addressed to achieve successful commercialization of this type of cell therapy. Finally, developments already on the horizon are discussed.


Regulation of matrix metalloproteinase-2 (gelatinase A, MMP-2), membrane-type matrix metalloproteinase-1 (MT1-MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line.
Soluble kappa-elastin peptides were shown to stimulate the expression of MMP-2 (but not MMP-9) by human fibrosarcoma HT-1080 cells, both at the protein and mRNA levels; maximal effect being observed at a concentration of 25 microg/ml of kappa-elastin. The stimulatory effect could be reproduced using Val-Gly-Val-Ala-Pro-Gly (VGVAPG) peptide, an elastin-derived hydrophobic hexapeptide which represented the elastin receptor binding sequence of tropoelastin. Furthermore, treatment of cells with lactose (30 mM), which dissociated 67-kDa elastin binding protein (EBP) from cell surfaces, completely abolished this effect, suggesting that the elastin receptor could mediate such a response. Using a specific monoclonal antibody, 67-kDa EBP was detected in HT-1080 membrane preparations by Western immunoblotting. Following treatment with 25 microg/ml kappa-elastin or 200 microg/ml VGVAPG, increased levels of the active 62-kDa form of MMP-2 were found in HT-1080 cell extracts. Stimulation of MT1-MMP mRNA expression by treatment with elastin-derived peptides (EDPs) was shown by competitive polymerase chain reaction (PCR). A reverse zymography analysis revealed that EDPs also stimulated TIMP-2 (but not TIMP-1) production by HT-1080 cells. Competitive PCR confirmed increased TIMP-2 mRNA expression by such treatment. These results suggest that occupancy of the 67-kDa elastin receptor by elastin-derived peptides enhanced both expression and activation of proMMP-2 and consequently, could promote the invasive/metastatic ability of tumor cells expressing this receptor.


Biologically Active Substance Content in Edible Plants of Zakarpattia and Their Elemental Composition Model.
Consumption of edible plants satisfies a significant part of human body needs in macro- and micronutrients while biologically active substances contain strong antioxidant properties and reduce the risk of a number of diseases. Balanced nutrition and design of personalized diets and treatment rely on the data on the content of macro- and micronutrients and biologically active substances. We determined polyphenol and anthocyanin content in 22 species of local edible plants using modified spectrophotometric method with Folin-Ciocalteu reagent as well as chemical elements' content in a mixture of edible plants from 13 regions using standard procedures. We performed correlational analysis of the obtained data and analysis of the main components in OriginLab, developed regional models of chemical elements' content for a mixture of edible plants, and conducted cluster analysis using common tools in Python. The results of biologically active substances' study demonstrated that the highest content of polyphenolic compounds and anthocyanins was found in grape meal of Vitis vinifera L. The study of chemical elements' content demonstrated that edible plants from lowland areas are the best and revealed clear dependences of the elements on each other and geographical conditions. The analysis of the principal components confirmed this finding. Based on the obtained data, a number of regional models of chemical elements' content in a mixture of edible plants were built, tested, and evaluated. Obtained results are the basis for designing various diets, filling composite databases of the region's food, and creating the newest biologics-pharmabiotics.


An in vivo comparison of acetate and palmitate as precursors of surfactant phosphatidylcholine.
3-Day-old rabbits were injected simultaneously with [(3)H]acetate and [(14)C]-palmitic acid. The specific activities of lung, lamellar body and surfactant phosphatidylcholine and disaturated phosphatidylcholine were measured at time intervals from 10 min to 23 h following isotope administration. Palmitic acid contained 87% of the acetate radioactivity recovered from lung and surfactant phosphatidylcholine. The relative specific activities of surfactant phosphatidylcholine and disturated phosphatidylcholine labeled with acetate were 2.02 and 1.86 times those measured using the palmitic acid label. Apparently the palmitic acid synthesized from acetate is preferentially incorporated into lung phosphatidylcholines and disaturated phosphatidylcholines which are destined to become surfactant.


Osteotome single-stage dental implant placement with and without sinus elevation: a clinical report.
Forty-three sites in 16 patients were selected for placement of implants using osteotomes in a single-stage surgical technique. Most sites were treated to enhance bone quality. Sixteen sites in the posterior maxilla had sinus elevation performed in conjunction with implant placement. No soft tissue coverage of the implant cover screw was attempted in either the sinus-elevated or the nonelevated sites. Sinus elevation was significant relative to baseline (mean gain 3.25 mm, P < .01). The implant survival rate was 95.3%.


Daffodil flowers delay senescence in cut Iris flowers.
Visible symptoms of tepal senescence in cut Iris x hollandica (cv. Blue Magic) flowers were delayed by placing one cut daffodil flower (Narcissus pseudonarcissus, cv. Carlton) in the same vase. Addition of mucilage, exuded by daffodil stems, to the vase water had the same effect as the flowering daffodil stem. The active compound in the mucilage was identified as narciclasine (using LC/MS, GC/MS, 1H and 13C-NMR, and comparison with an authentic sample of narciclasine). The delay of senescence, either by mucilage or purified narciclasine, was correlated with a delayed increase in protease activity, and with a considerable reduction of maximum protease activity. Narciclasine did not affect in vitro protease activity, but is known to inhibit protein synthesis at the ribosomal level. Its effects on senescence and protease activity were similar to those of cycloheximide (CHX), another inhibitor of protein synthesis, but the effective narciclasine concentration was about 100 times lower than that of CHX. It is concluded that the delay of Iris tepal senescence by daffodil stems is due to narciclasine in daffodil mucilage, which apparently inhibits the synthesis of proteins involved in senescence.


Effects of aggregation of red cells and linear velocity gradients on the correlation-based method for quantitative IVUS blood flow at 20 MHz.
Recent computer simulations suggest that the presence of aggregates of red blood cells (RBCs), at random angles and lengths, does not affect the measurements of blood flow transverse to the ultrasound (US) beam direction using a correlation-based method and an intravascular (IV) US array catheter. However, in case of aggregates of RBCs aligned with the flow, measurements of simulated blood velocity are affected. Blood velocity gradients were also shown not to influence the correlation-based method for blood velocity estimation. The objective of this study was to quantify the influence of aggregates of RBCs and blood velocity gradients on the correlation-based method during in vitro experiments. For this purpose, measurements were performed on washed RBCs (no aggregation), normal human blood, and two types of diseased blood in which a lower or a higher level of aggregation was present. The decorrelation pattern of a circular US transducer as a function of transverse blood flow was studied using a Couette system. Changing the shear rate of the Couette system modified the aggregation level of RBCs and the velocity gradient. With the exception of the results at low shear rates and abnormally high aggregation levels, agreements were found between the autoconvolution of the acoustical beam (reference curve) and the radiofrequency (RF) decorrelation patterns. For the high shear rate present in coronary arteries, the correlation-based method for blood flow estimation should not be influenced by these phenomena.


Blood vessels, a potential therapeutic target in rheumatoid arthritis?
New micro-vessels formation within synovium and macro-vessels endothelial damage with atheroma are two major features of rheumatoid arthritis, the former related to the articular involvement of the disease, the latter to its main systemic complication. The similarities between pannus development and solid tumors growth, and the efficacy of anti-angiogenic treatments in oncology, opened the perspective of directly targeting angiogenesis in arthritis. Nevertheless, despite the success of different anti-angiogenic therapeutic strategies in many arthritis experimental models, the application in human disease is still lacking. Recent data suggest that synovial neoangiogenesis and macro-vessels endothelial damage might be two linked phenomena. While synovial angiogenesis seems to be detrimental to endothelial damage repair, even anti-angiogenic treatments might paradoxically aggravate macro-vascular disease, especially in the context of uncontrolled inflammation. These elements induce to further explore the interconnections between inflammation and angiogenesis on one side and between micro- and macro-vascular diseases on the other, in order to establish the proper way to therapeutically target blood vessels in rheumatoid arthritis.


Two engineered AAV capsid variants for efficient transduction of human cortical neurons directly converted from iPSC.
Recombinant adeno-associated virus (AAV) is the most widely used vector for gene therapy in clinical trials. To increase transduction efficiency and specificity, novel engineered AAV variants with modified capsid sequences are evaluated in human cell cultures and non-human primates. We tested two novel AAV capsid variants, AAV2-NNPTPSR and AAV9-NVVRSSS, in human cortical neurons, which were directly converted from human induced pluripotent stem cells and cocultured with rat primary astrocytes. AAV2-NNPTPSR variant efficiently transduced both induced human cortical glutamatergic neurons and induced human cortical GABAergic interneurons. By contrast, AAV9-NVVRSSS variant transduced both induced human cortical neurons and cocultured rat primary astrocytes. High viral titers (1E+5 viral genomes per cell) caused a significant decrease in viability of induced human cortical neurons. Low viral titers (1E+4 viral genomes per cell) led to a significant increase in the neuronal activity marker c-Fos in transduced human neurons following treatment with a potassium channel blocker. We identified two engineered AAV capsid variants that efficiently transduce induced human cortical neurons. The threefold higher percentage of c-Fos positive, transduced human neurons may indicate functional alterations induced by viral transduction and/or transgene expression.


Recommendations for the management of hypokalemia in patients with cancer.
Hypokalemia is a common electrolyte disorder in cancer patients that may be associated with the primary disease or a complication of treatment. In this article, we provide a brief description of hypokalemia and its appropriate management in cancer patients.


Effect of diester and diether phosphatidylcholine on intestinal absorption of neutral and acidic sterols.
The effects of nondigestible diether phosphatidylcholine on intestinal absorption of cholesterol and dihydroxy and trihydroxy conjugated bile salts were studied in bile fistula rats using radioactive substrates. No inhibition of absorption of either dihydroxy or trihydroxy bile salts was observed. Nondigestible phospholipid did, however, significantly inhibit cholesterol absorption. Under control conditions with natural phosphatidylcholine in the intestinal perfusate, absorption of cholesterol was significantly greater when infused with taurocholate (TC) as compared to results obtained after infusion with taurochenodeoxycholate (TCD). Studies were repeated using radioactive rat liver phosphatidylcholine to determine whether the observed decrease in cholesterol absorption could be correlated with a decrease in digestion and absorption of rat liver phosphatidylcholine. No evidence was found for decreased absorption of this phospholipid when given with TCD. It is concluded that less cholesterol is absorbed in the presence of TCD as compared to TC, but the mechanism for this remains unexplained.


Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.
A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.


Induction of a secretory IgA response in the murine female urogenital tract by immunization of the lungs with liposome-supplemented viral subunit antigen.
This study demonstrates that liposomes administered to the lower respiratory tract of mice have the capacity to stimulate secretory IgA (s-IgA) antibody production in the female urogenital system. Total respiratory tract immunization of mice with influenza virus subunit antigen simply mixed with negatively charged liposomes induced antigen-specific s-IgA in vaginal secretions, in addition to systemic IgG and s-IgA in the respiratory tract. Immunization of the upper respiratory tract alone or oral immunization were ineffective. These observations demonstrate that, upon stimulation with liposomes, the lymphoid tissue associated with the lung can act as an inductive site for migration of IgA-committed B cells to distant mucosal tissues, including the female urogenital tract. It is concluded that liposomes administered to the lower respiratory tract provide a promising adjuvant system for stimulation of both systemic and mucosal antibody responses against coadministered antigen, including production of s-IgA at distant mucosal sites.


A dose escalating study of oxaliplatin and high dose weekly leucovorin and 5-Fluorouracil in patients with advanced solid tumors.
To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of L-OHP plus 5-FU and LV in patients with advanced solid malignancies. Patients received escalated doses of L-OHP (starting dose 50 mg/m2) as a 2-hour IV infusion on Days 1 and 15, and LV (500 mg/m2 as a 2-hour IV infusion) followed by escalated doses of 5FU (starting dose 1,800 mg/m2) as a 22-hour continuous IV infusion on Days 1, 8, 15, 21 every 6 weeks. DLTs were evaluated in the first cycle. Fifty-two patients [median age: 66 years; PS (ECOG) 0-1 in 90 percent] were treated on 12 dose-levels. Five (10 percent) patients had received 2 prior chemotherapy regimens, 24 (46 percent) one, and 23 (44 percent) were chemo-naïve. The DLT was reached at the dose of LOHP 100 mg/m2 and 5FU 2,200 mg/m2. Dose-limiting events were G3 diarrhea, G3 asthenia, G4 neutropenia, and G4 thrombocytopenia. Grade 3 diarrhea was observed in 6 (12 percent) patients and Grade 3 fatigue in 6 (12 percent). One (2 percent) patient developed Grade 4 neutropenia and another (2 percent) Grade 4 thrombocytopenia. The MTD were L-OHP 95 mg/m2 on d1 and d15 and 5FU 2,200 mg/m2/week for 4 consecutive weeks every 6 weeks.


[Ileostoma as part of a surgical therapy concept in acute pancreatitis].
14 patients with severe acute hemorrhagic pancreatitis underwent surgical procedure. In all patients besides intensive care and operative necrosectomy, lavage and drainage a loop ileostoma was installed. Pathophysiological considerations concerning the value of the loop ileostoma in the treatment of acute pancreatitis are discussed.


SARS-CoV-2 Variants: Mutations and Effective Changes.
One of the primary threats to the goal of controlling and eventually defeating SARS-CoV-2 is that of mutation. Recognizing this, a great amount of effort and dedicated study is being given to the matter. Due to the novel coronavirus's general prevalence and rate of mutation, this is an extremely dynamic area with constant new developments. Therefore, understanding the virus's pathogenesis and how mutations affect it is crucial. This review attempts to aid in understanding the currently most important strains and what primary changes they entail in connection to more specific mutations, and how they each affect infectivity, antigen resistance, and other properties. In an attempt to maintain relevance to the time at which this paper will be published, priority has been given to variants classified by the WHO and the CDC as of Sep. 23, 2021, as "Variants of Concern". Of particular interest in B.1.1.7, B.1.351, B.1.617.2, P.1 are the mutations affecting the Spike protein and Receptor Binding Domain, as they directly affect infectivity and susceptibility to neutralization. Certain mutations (D614G, E484K, N501Y, K417N, L452R and P681R) have appeared across several different strains, often accompanied by others that may be complementary working together to confer increased infectivity, fitness, or resistance to neutralization. We anticipate that the understanding of such COVID-19 mutations will, in the near future, prove important for diagnosis, treatment development, and vaccine development.


Drug and alcohol use by homicide victims in Trinidad and Tobago, 2001-2007.
This paper examines toxicology results from homicide victims in Trinidad and Tobago to explore patterns in pre-mortem drug and alcohol use. Toxicology test results were obtained for 1,780 homicide victims. Toxicology data from the coroner's office were linked with police data on homicide incidents to examine patterns in drug use and homicide. Trinidad and Tobago homicide victims tested positive for cannabis at a significantly higher rate (32%) than the average rate among other drug toxicology studies. Victims tested positive for alcohol (29%), cocaine (7%), and opioids (1.5%) at rates that were either comparable with or lower than those of homicide victims examined in other studies. The proportion of victims testing positive for cannabis grew significantly from 2001 to 2007; the proportions for alcohol and other drugs were fairly stable over time. Toxicology results also varied by homicide motive, weapon type, and the demographic characteristics of the victim. Toxicology data are a useful source for understanding patterns in drug use and homicide. Though such data have limitations, when combined with other types of data, they can often provide unique insights about a community's drug and violence problems.


Leishmania mexicana: effect of concomitant malaria on cutaneous leishmaniasis. Development of lesions in a Leishmania-susceptible (BALB/c) strain of mouse.
Effect of concomitant malaria on cutaneous leishmaniasis. Development of lesions in a Leishmania-susceptible (BALB/c) strain of mouse. Experimental Parasitology 65, 269-276. Symptoms of human leishmaniasis vary greatly, ranging from cryptic infections to cases with fatal sequelae. Factors regulating the severity of the disease are largely undetermined. Malaria coincides geographically with leishmaniasis in many areas and the immunosuppressive effects of malaria are well documented. It is therefore plausible that malaria could enhance the course of concomitant leishmaniasis. Interactions between Leishmania mexicana and Plasmodium yoelii were examined in BALB/c mice. Percentage of blood cells infected with P. yoelii and diameter of footpad lesions caused by L. mexicana were the criteria used to assay for disease severity. L. mexicana and P. yoelii infections were each significantly enhanced in dually infected mice when compared to mice infected with either parasite alone. Mortality rates due to the normally nonlethal P. yoelii were high during concurrent infections.


Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry.
1H Nuclear magnetic resonance (NMR) relaxometry was exploited to investigate the dynamics of solid proteins. The relaxation experiments were performed at 37 °C over a broad frequency range, from approximately 10 kHz to 40 MHz. Two relaxation contributions to the overall 1H spin-lattice relaxation were revealed; they were associated with 1H-1H and 1H-14N magnetic dipole-dipole interactions, respectively. The 1H-1H relaxation contribution was interpreted in terms of three dynamical processes occurring on timescales of 10-6 s, 10-7 s, and 10-8 s, respectively. The 1H-14N relaxation contribution shows quadrupole relaxation enhancement effects. A thorough analysis of the data was performed revealing similarities in the protein dynamics, despite their different structures. Among several parameters characterizing the protein dynamics and structure (e.g., electric field gradient tensor at the position of 14N nuclei), the orientation of the 1H-14N dipole-dipole axis, with respect to the principal axis system of the electric field gradient, was determined, showing that, for lysozyme, it was considerably different than for the other proteins. Moreover, the validity range of a closed form expression describing the 1H-14N relaxation contribution was determined by a comparison with a general approach based on the stochastic Liouville equation.


Retracted: Correlation between Pain Scores and Disc Height Changes after Discectomy in Patients with Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.
[This retracts the article DOI: 10.1155/2022/2580004.].


Frequency of BRCA1 and BRCA2 mutations in ovarian cancer patients in South-East Poland.
Mutations in BRCA1 and BRCA2 genes are well-established risk factors of breast and ovarian cancer. In our former study, we observed that approximately 6% of unselected ovarian cancer patients in the region of Podkarpacie (South-East Poland) carry BRCA1 causative founder variants, which is significantly lower than in other regions of Poland. Therefore, it is deeply justified to do research based on the sequencing of whole BRCA1 and BRCA2 genes. We examined 158 consecutive unselected cases of ovarian cancer patients from the region of Podkarpacie. We performed BRCA1 and BRCA2 genes Next-Generation Sequencing study in all cases. Altogether, in 18 of 158 (11.4%) ovarian cancer patients with BRCA1 or BRCA2 pathogenic mutations were found. BRCA1 pathogenic variants were detected in 11 of the 158 (7.0%) ovarian cancer cases. 10 of 11 (91%) detected BRCA1 mutations were founder mutations, detectable with the standard test used in Poland. BRCA2 pathogenic variants were found in 7 of the 158 (4.4%) cases. No BRCA2 pathogenic variants were founder mutations. The median age of patients at the diagnosis of the 18 hereditary ovarian cancers was 57.5 years. The frequency of BRCA1 or BRCA2 gene mutation carriers among patients with ovarian cancer from the Podkarpacie region is comparable to other regions of Poland. However, a significantly higher percentage of BRCA2 gene mutations was observed, that were not detectable with a standard test for detection of founder mutations. Diagnostics based only on testing the BRCA1/2 Polish founder mutations is characterized by relatively low sensitivity in the case of ovarian cancer patients from South-East Poland and should be supplemented by NGS study, in particular of the BRCA2 gene.


Ethanol differentially affects extracellular monoamines and GABA in the nucleus accumbens.
The magnitude, direction, and time course of the effects of acute administration of ethanol (0.1 or 1.0 g/kg) on the extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and GABA within the nucleus accumbens of the rat were analysed using microdialysis in conjunction with high-pressure liquid chromatography and electrochemical detection. IP injection of 0.1 g/kg ethanol failed to modify the extracellular concentration of DA, DOPAC, HVA, 5-HT, 5-HIAA, and GABA in the nucleus accumbens during the 120-min collection period. On the contrary, 1.0 g/kg IP ethanol significantly increased extracellular levels of DA, DOPAC, and 5-HIAA in microdialysates from the nucleus accumbens. The maximal increase in DA (314.87 +/- 6%), DOPAC (210.58 +/- 3%), and 5-HIAA (250.88 +/- 8%) was observed 40 min after administration of ethanol. Extracellular HVA was also enhanced (220.89 +/- 2%) at time point 100 min following injection of the same dose of ethanol. Finally, extracellular levels of 5-HT and GABA remained unchanged following 1.0 g/kg ethanol.


Biochemical assessment of thiamine nutrition in childhood.
The activity of red cell transketolase and TPP-effect were determined in 1028 infants and children, aged 1 month to 14 years, using a micromethod. All the children were healthy and without evidence of malnutrition. Transketolase activity decreased in the second year of life, followed by a constant increase up to the 6th year. Activity did not change in the next four years, then a steady decrease occurred. TPP-effect was not as stable as transketolase activity, and decreased significantly from years 3 to 5 and increased significantly from years 5 to 7. Beginning with year 10, TPP-effect decreased gradually. 6.6% of all children investigated had marginally deficient TPP-effects and 1.3% were biochemically deficient without clinical signs of avitaminosis. A group of 37 adults had transketolase activities and TPP-effect comparable to those of the 13 year-olds. Effect appeared to be marginal in 5.4% and deficient in 2.7%.


Biology and host range of Tecmessa elegans (Lepidoptera: Notodontidae), a leaf-feeding moth evaluated as a potential biological control agent for Schinus terebinthifolius (Sapindales: Anacardiaceae) in the United States.
During surveys for natural enemies that could be used as classical biological control agents of Schinus terebinthifolius Raddi (Brazilian pepper), the caterpillar, Tecmessa elegans Schaus (Lepidoptera: Notodontidae), was recorded feeding on the leaves of the shrub in South America. The biology and larval and adult host range of this species were examined to determine the insect's suitability for biological control of this invasive weed in North America and Hawaii. Biological observations indicate that the larvae have five instars. When disturbed, the late instar larvae emit formic acid from a prothoracic gland that may protect larvae from generalist predators. Larval host range tests conducted both in South and North America indicated that this species feeds and completes development primarily on members of the Anacardiaceae within the tribe Rhoeae. Oviposition tests indicated that when given a choice in large cages the adults will select the target weed over Pistacia spp. However, considering the many valued plant species in its host range, especially several North American natives, this species will not be considered further for biological control of S. terebinthifolius in North America.


Compression sclerotherapy: preparation, technique, complications, and results.
Compression sclerotherapy is not surgery-free, is not a cure, and rarely produces a "Hollywood leg". Repetitive injections are necessary for cosmetic control. The use of injection-compression for large thigh varicosities associated with saphenofemoral incompetency led to an inordinately high recurrence rate in this study, despite good initial results. By increasing the number of injections at the first session, 75 percent of the limbs were treated in a single session. The reinjection rate to maintain control was approximately 5 percent per year over the 7 year follow-up period. Compression sclerotherapy is an effective method of controlling venous perforators. Patients with bursting pain, severe signs of stasis, or ulceration are ideal candidates. It is particularly applicable to patients who are elderly, obese, or at high risk for other reasons and is a very useful tool in the management of venous disease. It is also very well accepted by patients. The technique should be more widely taught and practiced in North America.


Controlling Nutritional Status (CONUT) score as a prognostic marker for gastrointestinal stromal tumours.
The Controlling Nutritional Status (CONUT) score, regarded as the effective indicator of patient nutrition, has been demonstrated to be related to prognosis of numerous tumours. Nevertheless, the significance of CONUT for gastrointestinal stromal tumour (GIST) remains unclear. This study intended to clarify the association between CONUT and the prognosis of GISTs. Three hundred and fifty-five patients with GISTs undergoing surgical resection at our center were retrospectively assessed. Receiver operating characteristic curve analysis was used to help determine the cut-off value of CONUT score. Relapse-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier curve analysis. Prognostic factors for RFS and OS were examined by Cox proportional hazards models. A total of 355 patients were enrolled in this study. Areas under the curve (AUC) were 0.638 for CONUT score, and the cut-off value of CONUT was shown to be three. Kaplan-Meier curve analysis showed that high CONUT score was linked to poorer RFS and OS. Univariate and multivariate analyses ultimately revealed that CONUT was a risk factor for RFS and OS, independent of demographics and clinicopathological tumour characteristics. CONUT score was an effective and novel predictor for prognosis of GIST patients treated with surgery, indicating its potential as a prognostic marker in the overall management.


Glycosides from Buyang Huanwu Decoction inhibit atherosclerotic inflammation via JAK/STAT signaling pathway.
Buyang Huanwu Decoction (BYHWD) has been used to treat or prevent cardiovascular disease. The prescription and its glycosides have the effects of protecting blood vessels, and resisting atherosclerosis. However, their protective mechanism of anti-atherosclerosis remains unclear. This study aims to explore whether glycosides are the main effective components of BYHWD in anti-atherosclerotic inflammation and whether their mechanism is related to the classical JAK/STAT inflammatory signaling pathway. UPLC-MSMS method was used to determine the main components of BYHWD and its glycosides. Network pharmacological analysis and molecular docking were used to predict the potential therapeutic targets of glycosides. Atherosclerosis model was prepared by feeding HFD in ApoE-/- mice. The effects of glycosides on atherosclerosis were detected by blood lipids measurement, Masson staining, immunohistochemistry, immunofluorescence, western-blot and droplet digital PCR. RAW264.7 cells were used to establish foam cells model. The mechanism of glycosides anti-atherosclerotic inflammation was detected by measuring intracellular lipids, Oil Red O staining, ELISA, western-blot and droplet digital PCR. 1. Glycosides were absorbed into the blood through oral administrations and existed in the blood in the form of glycosides structures. 2. Glycosides attenuated hyperlipidemia, alleviated atherosclerotic lesions and inhibited inflammatory reaction. They could regulate blood lipids by decreasing TC, TG, LDL-c, increasing HDL-c level in ApoE-/- mice, alleviating intimal area and thickness, and inhibiting atherosclerotic plaque formation, which were similar to BYHWD. 3. Glycosides anti-atherosclerotic inflammation was related to JAK/STAT signaling pathway by network pharmacology analysis. Interactions between glycosides (astragaloside IV, paeoniflorin and amygdalin) and JAK/STAT pathway-related proteins by molecular docking. 4. Glycosides alleviated atherosclerotic inflammation by decreasing the release of pro-inflammatory factors and adhesions molecules, inhibiting the activation of JAK/STAT pathway in vivo. 5. Glycosides reduced the number of foam cells and intracellular lipid content. It also prevented the inflammation of macrophages by decreasing the levels of pro-inflammatory factors, reducing the phosphorylation of JAK2, STAT1 and STAT3 in vitro. This study demonstrated that glycosides were the main active components of BYHWD, and they could inhibit atherosclerosis by alleviating atherosclerotic inflammation. the mechanism is inhibiting the activation of JAK/STAT signaling pathway.


Effects of acute ureteral obstruction on glomerular hemodynamics in rat kidney.
In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a servo-nulling device, in control conditions and one to two hours after ureteral ligation. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentration. SNGFR was measured by conventional micropuncture techniques in control conditions and was calculated from efferent arteriole blood flow (EABF) and SNFF during ureteral obstruction. EABF was obtained by timed complete collection of blood from superficial efferent arterioles. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent arterioles (Re) were calculated from conventional equations. Ureteral obstruction markedly increased PT from 12.9 +/- 1.4 to 36.8 +/- 6.1 (SD) mm Hg. The fall in SNGFR (from 23.3 +/- 6.4 to 17.9 +/- 5.2 [SD] nl/min) was blunted by the rise in PG (from 45.5 +/- 3.6 to 59.3 +/- 4.0 [SD] mm Hg) and AABF (from 130.0 +/- 59.1 to 144.2 +/- 69.0 [SD] nl/min), secondary to a fall in Ra. These results demonstrate that SNGFR is maintained early after complete ureteral obstruction because of afferent arteriole dilatation.


The prognostic significance of the electrical QRS axis on long-term mortality in acute coronary syndrome patients - The TACOS study.
There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.


Organic horizon and mineral soil mercury along three clear-cut forest chronosequences across the northeastern USA.
Mercury (Hg) is a globally distributed pollutant trace metal that has been increasing in terrestrial environments due to rising anthropogenic emissions. Vegetation plays an important role in Hg sequestration in forested environments, but increasing tree removal for biofuels and wood products may affect this process. The long-term effect of clear-cutting on forest soil Hg remains uncertain, since most studies are limited to measuring changes for < 10 years following a single harvest event. The chronosequence approach, which substitutes space for time using forest stands of different ages since clear-cutting, allows for investigation of processes occurring over decades to centuries. Here, we utilized three clear-cut forest soil chronosequences across the northeastern USA to understand Hg accumulation and retention over several decades. Total Hg concentrations and pools were quantified for five soil depth increments along three chronosequences. Our results showed Hg concentrations and pools decreased in the initial 20 years following clear-cutting. Mineral soil Hg pools decreased 21-53% (7-14 mg m-2) between 1-5-year-old stands and 15-25-year-old stands but mineral soil Hg pools recovered in 55-140-year-old stands to similar values as measured in 1-5-year-old stands. Our study is one of the first to demonstrate a decrease and recovery in Hg pool size. These changes in Hg did not correspond with changes in bulk density, soil C, or pH. We utilized a simple two-box model to determine how different Hg fluxes affected organic and mineral soil horizon Hg pools. Our simple model suggests that changes in litterfall and volatilization rates could have caused the observed changes in organic horizon Hg pools. However, only increases in leaching could reproduce observed decreases to mineral soil Hg pools. Further studies are needed to determine the mechanism of Hg loss from forest soils following clear-cutting.


Exploring the application of sildenafil for high-fat diet-induced erectile dysfunction based on interleukin-18-mediated NLRP3/Caspase-1 signaling pathway.
Inflammation is a key risk factor for heart disease and has also been linked to erectile dysfunction (ED). Sildenafil is a phosphodiesterase type 5 inhibitor with a strong antioxidant effect. Interleukin (IL)-18 is a proinflammatory factor. Excessive production and release of IL-18 disrupt the balance between IL-18 and IL-18 binding proteins in certain inflammatory diseases, leading to the occurrence of pathological inflammation. We evaluated the effects of sildenafil on erectile function in a rat model of high-fat diet-induced ED. Male Sprague Dawley rats (6 weeks old) were divided into 5 groups: control, ED, sildenafil, IL-18, and IL-18 + sildenafil. Subsequently, intracavernous pressure and mean arterial pressure were used to assess the erectile function of these rats. The expression of endothelial nitric oxide synthase, pyroptosis factors, and the ratio of smooth muscle cells and collagen fibers were evaluated in the serum and corpora tissue. Exploring the role and mechanism of sildenafil in ED through NLRP3-mediated pyroptosis pathway. In comparison to the ED and IL-18 groups, there were statistically significant increases in the ratio of intracavernous pressure to mean arterial pressure, endothelial nitric oxide synthase expression, and the ratio of smooth muscle cells to collagen fibers following sildenafil intervention (P < .05). The sildenafil group and IL-18 + sildenafil group also showed statistically significant decreases the expression of NLRP3, caspase-1, and gasdermin D (P < .05). Sildenafil can improve erectile dysfunction by inhibiting inflammation. Strengths are that the relationship between pyroptosis and ED has been verified through in vitro and in vivo experiments. The limitation is that the conclusions drawn from animal and cells experiments need to be confirmed in clinical research. Sildenafil may reduce the effect of IL-18-induced inflammation in high-fat diet-induced ED rats through NLRP3/caspase-1 pyroptosis pathway.


Significance of IgM antibody to hepatitis B core antigen for the differential diagnosis of acute and chronic hepatitis B virus infection and for the evaluation of the inflammatory activity of type B chronic liver diseases.
IgM antibody to hepatitis B core antigen (anti-HBc) was assayed using a commercial kit in acute and chronic hepatitis B virus (HBV) infection and evaluated for its diagnostic and clinical significance. IgM anti-HBc was positive in all of 21 cases with type B acute hepatitis in the acute phase, and was also detected in 5 of 20 cases with type B chronic persistent hepatitis, in 4 of 20 patients with type B chronic active hepatitis and in one of 10 with type B liver cirrhosis. The absence of this marker was noted in all of 20 asymptomatic hepatitis B surface antigen (HBsAg) carriers and in 50 with HBsAg-negative patients with liver disease and in 200 healthy blood donors. The cut-off index of IgM anti-HBc was greater than 2.0 in all serum samples obtained in the acute phase of type B acute hepatitis, but was below 2.0 in type B chronic liver disease. A close relationship was found between the presence of IgM anti-HBc and the degree of inflammatory activity in patients with HBsAg-positive chronic liver disease. These data show that examination of IgM anti-HBc is useful in distingushing type B acute hepatitis from type B chronic liver disease, and also in evaluating the severity of disease in type B chronic liver disease.


Fresh Low Titer O Whole Blood Transfusion in the Austere Medical Environment.
Massive hemorrhage is an immediate threat to life. The military developed the Tactical Combat Casualty Care guidelines to address the management of acute trauma, including administration of blood products. The guidelines have been expanded to include low titer O whole blood, which is in limited use by the military. This proposal describes how the transfusion of fresh whole blood might be applied to the remote civilian environment. In doing so, this life-saving intervention may be brought to the austere medical environment, allowing critically hemorrhaging patients to survive to reach definitive medical care.


Validation of differences in backscatter coefficients among four ultrasound scanners with different beamforming methods.
The backscatter coefficient (BSC) indicates the absolute scatterer property of a material, independently of clinicians and system settings. Our study verified that the BSC differed among the scanners, transducers, and beamforming methods used for quantitative ultrasound analyses of biological tissues. Measurements were performed on four tissue-mimicking homogeneous phantoms containing spherical scatterers with mean diameters of 20 and 30 µm prepared at concentrations of 0.5 and 2.0 wt%, respectively. The BSCs in the different systems were compared using ultrasound scanners with two single-element transducers and five linear high- or low-frequency probes. The beamforming methods were line-by-line formation using focused imaging (FI) and parallel beam formation using plane wave imaging (PWI). The BSC of each system was calculated by the reference phantom method. The mean deviation from the theoretical BSC computed by the Faran model was analyzed as the benchmark validation of the calculated BSC. The BSCs calculated in systems with different properties and beamforming methods well concurred with the theoretical BSC. The mean deviation was below ± 2.8 dB on average, and within the approximate standard deviation (± 2.2 dB at most) in all cases. These variations agreed with a previous study in which the largest error among four different scanners with FI beamforming was 3.5 dB. The BSC in PWI was equivalent to those in the other systems and to those of FI beamforming. This result indicates the possibility of ultra-high frame-rate BSC analysis using PWI.


Hydatid detection using the near-infrared transmission angular spectra of porous silicon microcavity biosensors.
Hydatid, which is a parasitic disease, occurs today in many regions worldwide. Because it can present a serious threat to people's health, finding a fast, convenient, and economical means of detection is important. This paper proposes a label- and spectrophotometer-free apparatus that uses optical biological detection based on porous silicon microcavities. In this approach, the refractive index change induced by the biological reactions of a sample in a porous silicon microcavity is detected by measuring the change in the incidence angle corresponding to the maximum transmitted intensity of a near-infrared probe laser. This paper reports that the proposed method can achieve the label-free detection of 43 kDa molecular weight hydatid disease antigens with high sensitivity.


Numerical investigations of the bulk-surface wave pinning model.
The bulk-surface wave pinning model is a reaction-diffusion system for studying cell polarisation. It is constituted by a surface reaction-diffusion equation, coupled to a bulk diffusion equation with a non-linear boundary condition. Cell polarisation arises as the surface component develops specific patterns. Since proteins diffuse much faster in the cell interior than on the membrane, in the literature, the bulk component is often assumed to be spatially homogeneous. Therefore, the model can be reduced to a single surface equation. However, in real applications a spatially non-uniform bulk component might be an important player to take into account. In this paper, we study, through numerical computations, the role of the bulk component and, more specifically, how different bulk diffusion rates might affect the polarisation response. We find that the bulk component is indeed a key factor in determining the surface polarisation response. Moreover, for certain geometries, it is the spatial heterogeneity of the bulk component that triggers the polarisation response, which might not be possible in a reduced model. Understanding how polarisation depends on bulk diffusivity might be crucial when studying models of migrating cells, which are naturally subject to domain deformation.


Cross-cultural adaptation and validation of the cooking task to the French-Canadian context: assessing the impact of executive function disorders through cooking activities.
Acquired brain injury (ABI) often leads to deficits in executive functioning (EF) which is responsible for severe and longstanding disabilities in activities of daily living. The "Cooking Task" (CT), an ecological test of EF involving multi-tasking, was developed in France and exhibits excellent psychometric properties but has not yet been adapted and validated for the French-Canadian context. Conduct a cross-cultural adaptation and validation of the CT for the French-Canadian context. The CT was translated and adapted by a committee of experts and was validated. Adaptation-changes were made to the language (e.g., cartable vs classeur), the materials (e.g., measuring cup vs scale), and the measuring units (e.g., ml/cups vs grams). Validation-Preliminary analyses were conducted on 24 participants with an ABI and 17 controls. Construct convergent validity: The French-Canadian-CT discriminates between ABI and control total score on the CT and on most error type categories. Construct known-group validity: French-Canadian-CT scores correlated with another measure of EF deficits (Dysexecutive Questionnaire and Six Elements Task). Inter-rater reliability score for the total error was high (ICC= .84) and results were similar to those obtained for the France-CT. This study will provide a new ecologically valid tool for clinicians in Canada.


Role of farnesoid X receptor in hepatic steatosis in nonalcoholic fatty liver disease.
With the increased incidence of obesity, nonalcoholic fatty liver disease (NAFLD) has become a major global health concern. The pathogenesis of NAFLD has not yet been fully elucidated, and as few efficient pharmaceutical treatments are available for the condition, economic and medical burdens are heavy. Hepatic steatosis, as a precursor of NAFLD, plays a vital role in the pathological process of NAFLD. Hepatic steatosis is a consequence of lipid acquisition (i.e. free fatty acid uptake and de novo lipogenesis) exceeding lipid disposal (i.e. fatty acid oxidation and export as very-low-density lipoproteins). Therefore, restoring lipid homeostasis in the liver is an important therapeutic strategy of NAFLD. Farnesoid X receptor (FXR) is a major member of the ligand-activated nuclear receptor superfamily. Previous reviews have shown that FXR is a multipurpose receptor that plays an important role in regulating bile acid homeostasis, glucose and lipid metabolism, intestinal bacterial growth, and hepatic regeneration. This review focuses on the role of FXR in individual pathways that contribute to hepatic steatosis; it further demonstrates the molecular function of FXR in the pathogenesis of NAFLD.


Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives.
We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data, to find an effective antibacterial agent. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that the steroidal thiosemicarbazones derivatives inhibit growth of both types of the bacteria (Gram-positive and Gram-negative). The acetoxy and chloro derivatives of cyclopentyl and cyclohexyl amine thiosemicarbazones were found to have more antibacterial activity than the other derivatives.


Cesium attenuates conditioned avoidance response in rats and mice.
The pole-climbing conditioned avoidance response (CAR) was attenuated in rats after four once-daily injections of CsCl intraperitoneally at 3.0 mEq kg-1 and in mice after seven such injections at 5.0 mEq kg-1. Suppression of CAR increased with increasing numbers of injections. Treatment with cesium did not attenuate the unconditioned pole-climbing escape response to mild footshock. The cesium effect on CAR resembles that of antidopaminergic phenothiazine like agents, in concordance with our earlier studies which showed cesium potentiation of pentobarbital sleeping time and antagonism of amphetamine toxicity.


PROGINS receptor gene polymorphism is associated with endometriosis.
To investigate the association between the 306-base pair insertion polymorphism in intron G of the progesterone receptor (PROGINS) and endometriosis. Case-control study. Tertiary care center. Ninety-five white women with surgically diagnosed and histologically confirmed endometriosis and 107 white women without endometriosis (controls). Determination of PROGINS was performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and distribution of the PROGINS allele. Frequencies of the mutant allele T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio, 2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women with endometriosis and 0.9% of controls. PROGINS appears to be associated with endometriosis in white persons.


Unsettling care: Troubling transnational itineraries of care in feminist health practices.
Responding to the call by Maria Puig de la Bellacasa for Science and Technology Studies to take up 'matters of care', this article cautions against equating care with positive feelings and, in contrast, argues for the importance of grappling with the non-innocent histories in which the politics of care already circulates, particularly in transnational couplings of feminism and health. The article highlights these histories by tracing multiple versions of the politics of care in a select set of feminist engagements with the pap smear and cervical cancer. Drawing on postcolonial and indigenous feminist commitments, as well as amplifying Donna Haraway's call to 'stay with the trouble', the article seeks to disturb hegemonic histories and arrangements of race, colonialism, and political economy, while simultaneously valuing divergent multi-local itineraries as relevant to technoscientific matters of care. This call for a politics of 'unsettling' care strives to stir up and put into motion what is sedimented, while embracing the generativity of discomfort, critique, and non-innocence.


Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases.
Anticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines. To estimate timelines and probabilities of success for recent vaccine candidates. ClinicalTrials.gov was searched to identify trials testing viral vaccines that had not advanced to phase 2 before 2005, and the progress of each vaccine from phase 1 through to U.S. Food and Drug Administration (FDA) licensure was tracked. Trial characteristics were double-coded. (Registration: Open Science Framework [https://osf.io/dmuzx/]). Trials launched between January 2005 and March 2020. Preventive viral vaccine candidates for 23 emerging or reemerged viral infectious diseases. The primary end point was the probability of vaccines advancing from launch of phase 2 to FDA licensure within 10 years. In total, 606 clinical trials forming 220 distinct development trajectories (267 343 enrolled participants) were identified. The probability of vaccines progressing from phase 2 to licensure within 10 years was 10.0% (95% CI, 2.6% to 16.9%), with most approvals representing H1N1 or H5N1 vaccines. The average timeline from phase 2 to approval was 4.4 years (range, 6.4 weeks to 13.9 years). The probabilities of advancing from phase 1 to 2, phase 2 to 3, and phase 3 to licensure within the total available follow-up time were 38.2% (CI, 30.7% to 45.0%), 38.3% (CI, 23.1% to 50.5%), and 61.1% (CI, 3.7% to 84.3%), respectively. The study did not account for preclinical development and relied primarily on ClinicalTrials.gov and FDA resources. Success probabilities do not capture the varied reasons why vaccines fail to advance to regulatory approval. Success probabilities and timelines varied widely across different vaccine types and diseases. If a SARS-CoV-2 vaccine is licensed within 18 months of the start of the pandemic, it will mark an unprecedented achievement for noninfluenza viral vaccine development. McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding program.


Clinical and experimental studies on retinal neovascularization. XXXIX Edward Jackson Memorial Lecture.
Retinal neovascularization is a serious complication of the retinopathy associated with diabetes, branch vein occlusion, sickle cell anemia, and retrolental fibroplasia. Retinal capillary nonperfusion, demonstrated on fluorescein angiography, precedes the development of neovascularization in each of these conditions. Our working hypothesis is that the nonperfused (ischemic or hypoxic) retina liberates a vasoproliferative or angiogenic substance. Although I have delineated the clinical and experimental observations relating to the hypothesis of an ischemic-mediated angiogenesis substance, other postulated mechanisms for the development of retinal neovascularization may be involved. Recent observations on the experimental model of retrolental fibroplasia have demonstrated the markedly abnormal persistence and apparent proliferation of the hyaloid vessels in mice following oxygen-induced retinal vascular closure.


Fast analysis of flavonoids in plant extracts by liquid chromatography-ultraviolet absorbance detection on poly(carboxylic acid)-coated silica and electrospray ionization tandem mass spectrometric detection.
A highly hydrophilic poly(7-oxonorbornene-5,6-dicarboxylic acid-block-norbornene) [=poly-(ONDCA-b-NBE)]-coated silica was investigated for the liquid chromatographic (LC) determination of flavonoids in plant extracts of complex biological origin using UV absorbance and mass spectrometric (MS) detection. Compared to the most commonly used octadecyl derivatized silica this sorbent allowed fast separations even at extreme pH values. Furthermore, UV absorbance and MS detection were evaluated. As we found, UV detection at 254 nm allows the determination of flavonoids down to the ng range with a linearity of R2>0.9906. For the more selective characterization the validated LC system was coupled to a quadrupole ion trap mass spectrometer via an electrospray ionization (ESI) interface. MS detection showed high linearity (R2>0.9904) for all investigated flavonoids. Due to the relatively high flow-rate of 1 ml/min the limits of detection were found in the lower-microg range. Collision induced dissociation was applied to obtain characteristic fragmentation fingerprints. Finally, the validated LC-ESI-MS-MS method demonstrated that this poly-(ONDCA-b-NBE) stationary phase allows fast characterization and quantitation in onion, elderflower blossom, lime blossom, St. John's Wort and red wine.


The effectiveness of high-fidelity simulation methods to gain Foley catheterization knowledge, skills, satisfaction and self-confidence among novice nursing students: A randomized controlled trial.
The use of high-fidelity simulation (HFS) methods provides probable benefits and advantages for nursing students to retain knowledge, acquire skills, improve satisfaction, and gain self-confidence in a safe, realistic and supportive environment. To evaluate the effect of HFS methods to develop Foley catheterization knowledge, skills, satisfaction and self-confidence among novice nursing students when compared to low-fidelity simulation (LFS). The specific aim was to examine the effects of outcome variables between the intervention group and the control group, through multi-group path analysis. A randomized controlled trial was designed. 80 nursing students were randomly assigned to the HFS group (high-fidelity manikin and scenario) and the LFS group (female catheterization simulator) at a nursing faculty between May and July 2019 in Türkiye. The intervention group experienced HFS and the control group experienced LFS in order to learn Foley catheterization. Students' knowledge was evaluated before and after the intervention, while affective and psychomotor skills, and satisfaction and self-confidence in learning were evaluated after the intervention. The HFS group had better skill performance and significantly higher self-confidence in learning than the LFS group. While each group had a high level of knowledge, affective skills and satisfaction, there was no significant difference between the groups' mean scores. The HFS and scenario improved the knowledge, affective and psychomotor skills, satisfaction and self-confidence of novice nursing students on Foley catheterization. When compared to LFS, HFS had more advantages for the development of psychomotor skills and self-confidence in learning.


Pediatric parathyroid disease.
Parathyroid glands are critical for calcium and phosphate homeostasis. Parathyroid disease is relatively rare in the pediatric population, but there are some important pediatric-specific considerations and conditions. This article reviews parathyroid physiology, disorders of hyper- and hypo- function, operative management, and uniquely pediatric diagnoses such as neonatal severe hyperparathyroidism. Advances in preoperative imaging, intra-operative gland identification, and management of post-thyroidectomy hypocalcemia are also presented in detail. This article combines a review of fundamentals with recent advances in care, emphasizing pediatric-specific publications.


Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis and Mitral Regurgitation.
Many patients undergoing transcatheter aortic valve replacement (TAVR) for aortic stenosis also have significant mitral regurgitation (MR). We sought to understand the association of concomitant MR with TAVR clinical outcomes, as well changes in MR after TAVR. Patients who underwent TAVR in the US Transcatheter Valve Therapy Registry from January 3, 2012, to December 31, 2013, were studied, with longer-term clinical outcomes from Center for Medicare Services data. Of 11,104 patients, 3,481 (31.3%) had moderate MR, and 605 (5.5%) had severe MR. At 1 year, mortality was 21.0%, 21.5%, 26.3%, and 28.0% (p < 0.0001) and heart failure (HF) rehospitalization was 13.9%, 15.8%, 20.3%, and 23.4% (p < 0.0001) in the no, mild, moderate, and severe MR patients, respectively. After adjustment for baseline differences, significant MR was associated with increased risk of 1-year mortality or HF rehospitalization, with a HR of 1.16 (95% CI, 0.99 to 1.35) for moderate MR and 1.21 (95% CI, 0.97 to 1.50) for severe MR, compared with no MR. MR improved early after TAVR grade ≥ 1 in 79% of the severe MR patients and 66% of the moderate MR patients. Patients whose baseline moderate or severe MR improved had lower mortality (p = 0.022) and HF rehospitalization (p < 0.001) compared with patients whose MR did not improve. Moderate or severe MR accompanying severe AS treated with TAVR is associated with increased mortality or HF rehospitalization. This increased risk may be attributable to the minority of patients whose MR does not improve, suggesting a potential role for surveillance and targeted intervention for those patients.


Bronchoscopy with bronchoalveolar lavage in the evaluation of pulmonary complications of bone marrow transplantation in children.
Pulmonary complications are a frequent cause of morbidity and mortality following bone marrow transplantation. We examined the results of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) in 27 pediatric bone marrow transplant (BMT) recipients with 29 episodes of pulmonary complications. Bone marrow transplant was performed for a variety of malignancies and hematologic disorders. Median age of BMT was 10.3 years (range, 1.7-17.6 years). Median time of FB following BMT was 60 days (range, 11-1,026 days). Routine cytologic and culture techniques were utilized to detect malignant cells, viruses, fungi, bacteria, and protozoa. Positive results were found in 15 (52%) with cytomegalovirus (CMV), the most common positive finding. In 14 (48%) episodes the results were negative. Fourteen patients had follow-up autopsy or open lung biopsy (OLB). Based on autopsy/OLB results, there were two false negatives and no false positives, giving a diagnostic sensitivity of 75% and specificity of 100%. There was one possible complication of FB and BAL. Survival of both positive and negative patients was poor, only seven patients being alive 90 days post-FB with BAL. We conclude that FB with BAL is a safe and accurate procedure for the diagnosis of pulmonary complications of BMT.


Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications.
Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180-4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3-18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12-31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.


Forage Yield, Canopy Characteristics, and Radiation Interception of Ten Alfalfa Varieties in an Arid Environment.
An increasing demand for new and improved livestock forage products is driving the development of forage systems in arid regions. Our study evaluated the productivity of 10 alfalfa (Medicago sativa L.) varieties and the relationship between forage yield and canopy structure traits, such as plant height, branch number, stem/leaf ratio, and leaf area index in the arid Hexi Corridor, north-west China. Here, plant height, primary branch number per plant, and stem/leaf ratio were positively correlated with forage yield. In terms of a two-year total yield, Gannong No. 5 produced the highest value (13,923 kg ha-1), followed by the WL342HQ (12,409 kg ha-1), Phabulous (11,928 kg ha-1), and Xinjiang Daye (11,416 kg ha-1) varieties. Therefore, these four alfalfa varieties are suitable for large-scale cultivation in the Hexi Corridor region and other arid areas where the effect of precipitation is even larger than that of temperature. These results provide valuable information for the selection and cultivation of alfalfa varieties, which could improve forage yield and the production of livestock in arid regions.


Pharmaceuticals in water as emerging pollutants for river health: A critical review under Indian conditions.
The wastewaters from pharmaceutical manufacturing units, hospitals, and domestic sewage contaminated with excretal matters of medicine users are the prime sources of pharmaceutical pollutants (PPs) in natural water bodies. In the present study, PPs have been considered one of the emerging pollutants (EPs) and a cause of concern in river health assessment. Beyond the reported increase in antibiotic-resistant bacteria (ABRB), PPs have been found adversely affecting the biotic diversity in such water environments. Considering Algae, Macroinvertebrates, and Fishes as three distinct trophic level indicators, the present study puts forward a framework for showing River Health Condition (RHC) based on the calculation of a River Health Index (RHI). The RHI is calculated using six Indicator Group Scores (IGS) which individually reflect river health in a defined category of water quality characteristics. While Dissolved Oxygen Related Parameters (DORP), Nutrients (NT), and PPs are taken as causative agents affecting RHCs, scores of Algal-Bacterial (AB) symbiosis, Macroinvertebrates (MI), and Fishes (F) are considered as an effect of such environmental conditions. Current wastewater treatment technologies are also not very effective in the removal of PPs. The objective of the present study is to review the harmful effects of PPs on the aquatic environment, particularly on the chemical and biotic indicators of river health. Based on predicted no-effect concentrations (PNEC) for algae, macroinvertebrates, and fishes in the aquatic environment and measured environmental concentration (MEC) in the river, the estimated risk quotient (RQ) for norfloxacin in the Isakavagu-Nakkavagu stream of river Godavari, Hyderabad is found 293 for algae, 39 for MI, and 335 for fish. Among PPs, in Indian rivers, the presence of caffeine is the most frequent, with algae at the highest level of risk (RQmax= 24.5). Broadly six PPs, including azithromycin, caffeine, diclofenac, naproxen, norfloxacin, and sulfamethoxazole are found above PNEC values in Indian rivers. The application of IGS and RHI in understanding and presenting the river health condition (RHC) through colored hexagons has been demonstrated for the river Ganga near Varanasi (India) as an example. Identification of critical indicator groups, based on IGS provides a scientific basis for planned intervention for river health restoration to achieve an acceptable category.


Assessment of oxygen-consumption by use of reverse Fick-principle and indirect calorimetry in critically ill patients.
Oxygen consumption was measured simultaneously by the reverse Fick-principle (V02FICK) and by indirect calorimetry ("Metabolic Measurement Cart Horizon") (V02MMC) in 31 critically ill patients; 24 men and 7 women. Seventeen patients were breathing spontaneously, 14 patients were on mechanical ventilation. The fractional inspiratory oxygen concentration (FI02) in ventilated patients ranged from 0.21 to 0.4 (mean 0.302). Total oxygen consumption as measured by indirect calorimetry was 286.7 +/- 59.7 ml/min (mean +/- SD), and measured by reverse Fick-principle 258.9 +/- 52.2 ml/min (mean +/- SD). The coefficient of correlation between the two methods was r = 0.873. The absolute difference of oxygen consumption between reverse Fick-method and indirect calorimetry was 11.3%. Regression analysis according to Theil revealed a similar regression between spontaneously breathing and mechanically ventilated patients for the studied FI02 values below 0.4. It is concluded that indirect calorimetry is a reliable method for measuring oxygen consumption in spontaneously breathing as well as mechanically ventilated critically ill patients.


Final report from the Committee on Antimicrobial Susceptibility Testing, Japanese Society of Chemotherapy, on the agar dilution method (2007).
In 1968, the agar dilution method was developed as an independent Japanese method for measuring the minimal inhibitory concentration (MIC) of antimicrobial agents. As this method differed in a few respects from the MIC measurement methods used in other countries, it was revised in 1981, by a committee headed by Susumu Mitsuhashi, and the revised method (Chemotherapy 29:76-79, 1981) has been used since then. In 1979, an agar dilution method for measuring the MIC of anaerobes was developed by a committee chaired by Nozomu Kosakai (Chemotherapy 27:559-561, 1979). In 1990, a committee headed by Sachiko Goto approved a broth microdilution method for nonfastidious bacteria (Chemotherapy 38:102-105, 1990). Later, a committee headed by Atsushi Saito examined media that would be suitable for nonfastidious bacteria and fastidious bacteria, and they endeavored to prepare a broth microdilution method for anaerobic bacteria. In this context, a new broth microdilution method was proposed at the 40th Annual Meeting of the Japanese Society of Chemotherapy (JSC) in Nagoya in 1992, and the proposal was adopted as the standard JSC method after some modification (Chemotherapy 41: 183-189, 1993). The agar dilution method has remained unrevised for approximately 20 years. A proposal to review this method was recently made, and the 2007 Committee on Antimicrobial Susceptibility Testing was formed, comprising the JSC members listed below. Under the auspices of this committee, the method revised in 1981 was reviewed in comparison to the international standard method (Clinical and Laboratory Standards Institute [CLSI] method).


Practical denture disinfection.
Dental laboratory personel are at risk of contracting infections from dental prostheses that have not been properly disinfected. A 4% chlorhexidine scrub for 15 seconds followed by a 3-minute contact time with a chlorine dioxide solution was effective in disinfecting contaminated dentures. Chair-side disinfection of dental prostheses before laboratory procedures is the key to keeping microbial contamination out of the dental laboratory.


The rim area of the optic nerve head, assessed with Heidelberg retina tomography, is smaller in prematurely born children than in children born at term.
To examine the optic nerve head with Heidelberg tomography (HRT) in prematurely born school-age children and compare them to children born at term. Sixty-three 5-16-year-old children born with a gestational age (GA) of ≤32 weeks were included in the study and compared to 54 children of the same age, born at term. In the preterm group, 29 children had had retinopathy of prematurity (ROP) and nine children had neurological complications. The optic nerve head was assessed with HRT. Three measurements were performed, and the different topographic parameters were noted. Rim area of the optic nerve was significantly smaller in prematurely born children than in children born at term. The mean difference was 0.146 mm2 (p = 0.02). No difference between the groups was found regarding disc area or cup area. In the preterm group, both disc and rim areas were reduced with increasing GA. No correlations with birthweight, ROP or neurological complications were found. Reduced rim area of the optic nerve head was found in preterm children of school age. Previous ROP or neurological complication did not influence the result, suggesting the preterm birth per se was the reason for the reduction. Establishing whether this finding was caused by disturbed maturation of the optic nerve or by injury of the axons, or a combination of the two, will require further research.