Open abdomen in the trauma ICU patient: who? when? why? and what are the outcome results?
Temporary abdominal closure is a component of damage control surgery and may decrease mortality rates. The ultimate aim in managing an open abdomen is to achieve definitive fascial closure. The aim of this study is to assess the previously known predictors for failure to achieve definitive fascial closure and identify new predictors in order to achieve a better outcome. An 11-year retrospective chart review included open abdomen cases at Inkosi Albert Luthuli Hospital Trauma ICU in KZN (Ethics Approval BCA207-09). The evaluated outcomes were definitive fascial closure, open abdomen and mortality. Variables included age, co-morbidities, albumin levels, renal failure, multiple blood transfusions, type of blood products given, entero-atmospheric fistulas, TAC, anastomosis, intra-abdominal abscess, type of nutrition, ACS, number of re-laparotomies, deep site infections (peritonitis), systemic infections (bloodstream), ventilator acquired pneumonia, head injury, and type of fluids given. This study reviewed 188 cases, 46.8% (88) arrived from elsewhere with an open abdomen while 53.2% (100) did not; 46.8% suffered blunt trauma, 45.2% suffered gunshots, while 8.0% were stabbed. Ninety deaths (47.9%) occurred during the index admission with 57 (30.3%) within the first 30 days. For both death within 30 days and death as final outcome, the majority were blunt abdominal trauma, 51.1 and 52.6%, respectively. Out of 188 patients, 27.1% had definitive fascial closure and 26.6% remained with an open abdomen. The relevant variables related to failure to achieve fascial closure were hypoalbuminemia (p = 0.002, p = 0.036), anastomotic leak (p < 0.05), VAP (p = 0.007), age (p = 0.002), intra-abdominal abscesses (p = 0.006), ACS (p = 0.005), multiple re-laparotomies (p = 0,028), deep surgical site infection (p < 0.05) and multi-organ failure (p = 0.003). This study identified the predictors of failed fascial closure and mortality. While not directly modifiable, hypoalbuminaemia, anastomotic leak and sepsis, leading to multiple re-laparotomy, preclude early closure and portend high mortality.


The state of the renin-angiotensin-aldosterone system in various clinical forms of hypertension in aging.
The authors' data give evidence for an early involvement of the renin-angiotensin-aldosterone system in the hypertension pathogenesis with aging. The elderly patients with the systolic hypertension variant showed marked hyporeninemia and hyperaldosteronemia, while those with the systolic-diastolic variant displayed an increased or normal plasma renin activity against moderately increased aldosterone concentration. There was a marked increase of plasma renin activity in the patients with the cardiac form and a high circulating aldosterone concentration with the cerebral form of hypertension. The results suggest a certain interrelationship between the clinical picture of the disease and the renin-angiotensin-aldosterone system. The latter must be taken into consideration when making decisions regarding therapy and prophylaxis of hypertension.


Transitions in intronic regions result in two novel HLA-DQB1 alleles: -DQB1*05:02:01:13 and -DQB1*05:02:01:14.
Two transitions in intronic regions give rise to the novel alleles: HLA-DQB1*05:02:01:13 and HLA-DQB1*05:02:01:14.


DNA damage and repair in gastric cancer--a correlation with the hOGG1 and RAD51 genes polymorphisms.
The cell's susceptibility to mutagens and its ability to repair DNA lesions are important for cancer induction, promotion and progression. Both the mutagens' sensitivity and the efficacy of DNA repair may be affected by variation in several genes, including DNA repair genes. The hOGG1 gene encodes glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both can be involved in the repair of oxidative DNA lesions, which can contribute to stomach cancer. In the present work we determined the level of basal and oxidative DNA damage and the kinetics of removal of DNA damage induced by hydrogen peroxide in peripheral blood lymphocytes of 30 gastric cancer patients and 30 healthy individuals. The metrics from DNA damage and repair study were correlated with the genotypes of common polymorphisms of the hOGG1 and RAD51 genes: a G-->C transversion at 1245 position of the hOGG1 gene producing a Ser-->Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G-->C substitution at position 135 (5'-untranslated region) of the RAD51 gene (the G135C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis (comet assay) assisted by DNA repair enzymes: endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), preferentially recognizing oxidized DNA bases. The genotypes of the polymorphism were determined by restriction fragment length polymorphism PCR. We observed a strong association between gastric cancer occurrence, impaired DNA repair in human lymphocytes and the G/C genotype of the G135C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and stomach cancer occurrence in subjects with high level of oxidatively damaged DNA. We did not observe any correlation between the Ser1245Cys polymorphism of the hOGG1 gene and gastric cancer, including subjects with impaired DNA repair and/or high levels of endogenous oxidative DNA lesions. Therefore, our result suggest that the G135C polymorphism of the RAD51 gene may be linked with gastric cancer by the modulation of the cellular response to oxidative stress and this polymorphism may be a useful additional marker in this disease along with the genetic or/and environmental indicators of oxidative stress.


A cannulated probe for torn inferior canaliculus repair.
A cannulated probe and silicone tube for the repair of the torn inferior canaliculus are described and illustrated.


An exploratory analysis of factors associated with weight change in a 16-week trial of oral vs. orally disintegrating olanzapine: the PLATYPUS study.
We conducted exploratory analyses of the data from a multinational, randomised study to identify factors associated with weight change after 16 weeks of treatment with standard olanzapine tablets (SOT) or sublingual orally disintegrating olanzapine (ODO). One hundred and forty nine outpatients who gained weight during prior SOT therapy were enrolled into the study and treated with ODO (N = 84) or SOT (N = 65). Exploratory analyses were conducted with the subset of compliant patients (ODO: n = 60; SOT: n = 47). The decrease in the rate of weight gain at the end of study therapy (change from baseline) was greater in the ODO group than the SOT group (-0.59 kg/week vs. -0.38 kg/week, p = 0.0246). Age was negatively associated with weight change (p = 0.0203) in both treatment groups combined: patients gained 0.7 kg less for every 10 years of age. The least squares mean weight gain was lower with ODO than SOT in male patients (0.35 kg vs. 3.04 kg, p = 0.061), but not female patients and in American patients (0.55 kg vs. 6.21 kg, p < 0.0001), but not Canadian or Mexican patients. Although not conclusive, these data suggest that ODO may be a reasonable treatment option for some patients who gain weight with SOT. Further research is required to confirm these findings.


Transport of membrane-bound macromolecules by M cells in follicle-associated epithelium of rabbit Peyer's patch.
M cells in Peyer's patch epithelium conduct transepithelial transport of luminal antigens to cells of the mucosal immune system. To determine the distribution of specific lectin-binding sites on luminal membranes of living M cells and to follow the transport route of membrane-bound molecules, lectin-ferritin conjugates and cationized ferritin were applied to rabbit Peyer's patch mucosa in vivo and in vitro. The degree to which binding enhances transport was estimated by comparing quantitatively the transport of an adherent probe, wheat germ agglutinin-ferritin, to that of a nonadherent BSA-colloidal gold probe. When applied to fixed tissue, the lectins tested bound equally well to M cells and columnar absorptive cells. On living mucosa, however, ferritin conjugates of wheat germ agglutinin and Ricinus communis agglutinins I and II bound more avidly to M cells. Absorptive cells conducted little uptake and no detectable transepithelial transport. Lectins on M cell membranes were endocytosed from coated pits, rapidly transported in a complex system of tubulocisternae and vesicles, and remained adherent to M cell basolateral membranes. Cationized ferritin adhered to anionic sites and was similarly transported, but was released as free clusters at M cell basolateral surfaces. When applied simultaneously to Peyer's patch mucosa, wheat germ agglutinin-ferritin was transported about 50 times more efficiently than was bovine serum albumin-colloidal gold.


Excessive fecal taurine loss predisposes to taurine deficiency in cystic fibrosis.
Elevation of the ratio of glycine: taurine-conjugated bile acids (G/T ratio) is thought to contribute to fat malabsorption in cystic fibrosis (CF). The cause, extent, and reversibility of taurine deficiency in CF were assessed using balance studies in 6 subjects (ages 8-14 years) who were supplemented with taurine (0.24-2.4 mmol/kg/24 h) for 1 week. Taurine reduced the G/T ratio both in serum and duodenal juice in all children. The mean fecal taurine loss in CF subjects [10.8 mumol/kg/24 h +/- 9.9 (SD), range 0.9-27.9] was much greater than that in controls (less than 0.1 mumol/kg/24 h, n = 4) and approximated the dietary taurine intake (mean 14.6 +/- 4.4 mumol/kg/24 h, n = 12). Absorption of an oral taurine load appeared to be normal in CF. Excessive fecal taurine loss appears to predispose CF children to bile acid taurine deficiency, a deficiency that can be corrected by oral taurine supplements.


Effect of adhesion or collagen molecules on cell attachment, insulin secretion, and glucose responsiveness in the cultured adult porcine endocrine pancreas: a preliminary study.
The effect of either adhesion or collagen molecules on cell attachment, insulin secretion, and glucose responsiveness was investigated in adult porcine pancreatic endocrine (PE) cells that were cultured for a longer term in vitro. Six different types of molecules--laminin, fibronectin, poly-L-lysine (PLL), type I collagen, gelatin, and Matrigel--were used. Approximately 2.0 x 10(5) cells per dish of each molecule type were cultured for 4 weeks. In the laminin group, the insulin accumulation was maintained at a significantly higher level than in the control group at 4 weeks of culture, and glucose-stimulated insulin secretion and the insulin-positive rate were also higher than in the control group. In the Matrigel group, islet-like cell clusters were formed, but insulin accumulation rapidly decreased at 3-4 weeks of culture. A large number of PE cells attached tightly and spread in the fibronectin group until the fourth week of culture, but their function was not better than those in the control group. In the PLL and gelatin groups, the PE cell function was not significantly different from that of the control group. In the type I collagen group, insulin secretion was inferior to that of the other groups. The results of this study suggest that laminin is the most suitable extracellular matrix for the long-term culture preservation of PE cells.


SR 141716A differentially attenuates the behavioral effects of delta9-THC in rhesus monkeys.
The prototypic cannabinoid CB1 antagonist SR 141716A is one important pharmacologic tool for examining CB1 receptors that mediate the behavioral and physiologic effects of delta9-tetrahydrocannabinol (delta9-THC). This study examined the effects of SR 141716A on the rate-decreasing, hypothermic and discriminative stimulus effects of delta9-THC in rhesus monkeys. In monkeys (n=4) responding under a multiple fixed ratio (FR-10:FR-10) schedule of food presentation and stimulus-shock termination, the potency of i.m. delta9-THC to decrease responding in the food component (ED50=0.64 mg/kg) was threefold greater than its potency in the stimulus-shock termination component (ED50=2.14 mg/kg). In the same monkeys, hypothermia was induced by delta9-THC at a dose (e.g. 0.32 mg/kg) that did not alter responding in either schedule component; the maximum decrease was 2.1 degrees C at a dose of 3.2 mg/kg. A dose of 0.32 mg/kg of SR 141716A, significantly attenuated delta9-THC-induced hypothermia without attenuating the rate-decreasing effects of delta9-THC in either component of the multiple schedule. The largest dose of i.m. SR 141716A that was studied, 1.0 mg/kg, significantly decreased rectal temperature and responding in the food component but did not significantly decrease responding in the stimulus-shock termination component of the multiple schedule. In a separate group of monkeys (n=3) that discriminated i.v. delta9-THC (0.1 mg/kg) while responding under an FR-5 schedule of stimulus-shock termination, SR 141716A (0.32 and 1 mg/kg) significantly increased the ED50 of the delta9-THC by 2.3- and 3.7-fold, respectively. Collectively, these results demonstrate that the behavioral effects of delta9-THC are not equally attenuated by SR 141716A.


Positive correlation of gene expression between branchial FXYD proteins and Na+/K+-ATPase of euryhaline milkfish in response to hypoosmotic challenges.
FXYD proteins are crucial regulators of Na+/K+-ATPase (NKA), which plays an important role in ion exchange by providing the driving force for other ion-transporting systems in the osmoregulatory organs, including the gills. In milkfish (Chanos chanos), gill NKA has been widely investigated and found to alter its expression (both mRNA and protein) and activity in response to environmental salinity changes. However, the expression and roles of the regulatory proteins of NKA, the FXYD proteins, in milkfish gills upon salinity challenge is not yet clear. Hence, this study illustrated the potential roles of milkfish branchial FXYD proteins in modulating NKA expression via identification and tissue distributions of FXYD proteins, as well as the effects of salinity on expression of gill fxyd and nka mRNA. Six milkfish FXYD proteins (CcFXYD) were identified. In milkfish gill, gill-specific Ccfxyd11 was the predominant member, followed by Ccfxyd9 and Ccfxyd8. Upon hypoosmotic challenges, increases in gill Ccfxyd11, Ccfxyd8, Ccnka α1, and Ccnka β1 mRNA as well as significantly positive correlations were observed. Moreover, after acute salinity changes, expression of gill Ccfxyd11 and Ccnka was found to change with ambient salinity, and significant positive correlations were also exhibited between Ccfxyd11 and Ccnka α1. Overall, these results revealed close relationships between CcFXYD11 and CcNKA α1 in milkfish gills, highlighting the potential roles of CcFXYD11 in osmoregulation.


Presence of Fibroids on Transvaginal Ultrasonography in a Community-Based, Diverse Cohort of 996 Reproductive-Age Female Participants.
Fibroids are benign uterine tumors that can cause significant morbidity. Knowledge on fibroid prevalence, especially in the asymptomatic population and in Asian and Hispanic or Latina individuals, is limited, and a better understanding of affected groups will improve timely diagnosis and motivate appropriate recruitment in clinical trials to reduce health disparities. To estimate the prevalence of fibroids in a diverse cohort of female individuals. This cross-sectional study included female individuals not seeking treatment for fertility or other conditions who were prospectively recruited in an academic medical center in San Francisco, California. Effort was made to recruit an equal proportion of participants from 4 large racial and ethnic groups in the United States (Asian-Chinese, Black or African American, Hispanic or Latina, and White) and across 4 equal age groups between 25 and 45 years. All participants reported regular menses (21-35 days), had not used estrogen- or progestin-containing medications in the 3 months prior to enrollment, and denied history of pelvic surgery. The assessment of ultrasonography results was part of an ongoing longitudinal cohort, with initial recruitment from October 2006 to September 2012. Data analysis was performed in April to September 2022. Fibroid presence and burden as assessed by transvaginal ultrasonography. A total of 996 female participants were included in the analysis, including 229 (23.0%) Asian-Chinese, 249 (25.0%) Black or African American, 237 (23.8%) Hispanic or Latina, and 281 (28.2%) White individuals. Mean (SD) age was 34.8 (5.7) years in Asian-Chinese participants, 35.4 (6.1) years in Black or African American participants, 34.8 (5.3) years in Hispanic or Latina participants, and 35.3 (5.0) years in White participants. Fibroids were present in 21.8% (95% CI, 16.7%-27.8%) of Asian-Chinese participants, 35.7% (95% CI, 29.8%-42.0%) of Black or African American participants, 12.7% (95% CI, 8.7%-17.6%) of Hispanic or Latina participants, and 10.7% (95% CI, 7.3%-14.9%) of White participants. Black or African American and Asian-Chinese participants were more likely to have fibroids than White participants (Black or African American: adjusted odds ratio [OR], 4.72 [95% CI, 2.72-8.18]; P < .001; Asian-Chinese: adjusted OR, 3.35 [95% CI, 1.95-5.76]; P < .001). In those with fibroids, the proportion with multiple fibroids were 48.3% in Black or African American participants, 33.3% in White participants, 33.3% in Hispanic or Latina participants, and 26.0% in Asian-Chinese participants (P = .06). The largest mean (SD) fibroid diameter was 3.9 (1.9) cm in Black or African American participants, 3.2 (1.6) cm in Asian-Chinese participants, 3.2 (1.6) cm in White participants, and 3.0 (1.4) cm in Hispanic or Latina participants (P = .03). In this study of female participants in a nonclinical setting, Black or African American and Asian-Chinese participants were disproportionately affected by uterine fibroids. Hispanic or Latina participants had similar fibroid burden to White participants.


Unsuspected urethral stricture presenting as acute water intoxication.
We report a case of an unsuspected urethral stricture that caused acute water intoxication with generalized convulsions. The patient drank excessive amounts of water in an attempt to relieve obstruction. Osmolality, water balance and renal function returned to normal after relief of obstruction. A urethral stricture should be considered in the diagnosis of a patient with severe dilutional hyponatremia.


Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report.
Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.


Atypical depression in children and adolescents.
Major depressive disorder (MDD) with atypical features has been described in adults. Furthermore, several studies have suggested that tricyclic antidepressants were less effective for MDD with atypical features than for MDD without atypical features. Thus, it may be important to determine whether atypical features are present in MDD. To date, only one study has examined the diagnosis of depression with atypical features in children and adolescents by using the DSM-IV criteria. Current knowledge suggests the DSM-IV criteria for depression with atypical features in children and adolescents may need to be reconsidered, as biological, hormonal, developmental, and psychological factors in this age group may be different from those of adults with atypical depression.


Validation of the Turkish version of "Test for Respiratory and Asthma Control in Kids (TRACK)" questionnaire.
Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire is the first to measure both the risk and impairment domains of the current guidelines in preschool children. We aimed to measure the reliability, validity and responsiveness of the Turkish version of the TRACK. A total of 268 children (69.8% boys) were included in the study. Caregivers responded to three individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and 3rd month). At each visit, physicians determined the control level and the treatment strategy based on the GINA guideline recommendations. The internal consistency reliability of the Turkish version of the TRACK questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits, respectively (reliability statistics, Cronbach's alpha). There was a significant difference between the mean TRACK scores of the patients in different asthma control status categories (p < 0.001). The test-retest reliability in stable patients was 0.90. The optimal cut-off scores according to the Youden index were 80 and 60 points for uncontrolled and very poorly controlled children, respectively. The Turkish version of the TRACK is an accurate and reliable tool for evaluating asthma control status among preschool Turkish children. Its widespread use may help physicians correctly assess control levels among children and may improve the quality of life for both patients and their caregivers.


North Carolina hospital redefines itself as critical-access facility. Bertie Memorial called a national model.
Bertie Memorial Hospital. Windsor, N.C., is redefining itself in its new home as a national model for critical-access hospitals designated by the federal Office of Rural Health Policy. The hospital recently opened a new $10 million, 48,000-square-foot, state-of-the-art facility.


Factors controlling mercury and methylmercury concentrations in largemouth bass (Micropterus salmoides) and other fish from Maryland reservoirs.
The concentration of mercury (Hg) and methylmercury (MeHg) was determined for largemouth bass (Micropterus salmoides), bluegill (Lepomis macrochirus) and black crappie (Pomoxis nigromaculatus) from Maryland reservoirs. Overall, there was a large difference in normalized bass MeHg concentration (for fish of approximately 370 mm) between the reservoirs, ranging from <100 ng g(-1) to almost 800 ng g(-1). Furthermore, the relationship between fish weight and MeHg concentration varied substantially between lakes, and showed no geographical relationship. The concentration of Hg, MeHg and ancillary parameters were determined in the water and correlations were sought between the normalized concentration of MeHg in bass and both physical and chemical parameters of the reservoirs, as well as the concentration of MeHg in the prey of the largemouth bass. Bass MeHg concentration correlated with dissolved MeHg and dissolved organic carbon, but not with other chemical parameters. There was no relationship to physical characteristics that varied over orders of magnitude for these reservoirs. Dissolved MeHg did not correlate with any chemical or physical attributes. Overall, this study suggests that water column MeHg is a good predictor of fish concentration but that the water column MeHg cannot be predicted based on usually measured chemical and physical characteristics of fresh water bodies.


Perioperative outcomes using LigaSure™ compared to conventional bipolar instruments in laparoscopic salpingo-oophorectomy: a randomized controlled trial.
The aim of this study was to compare the effects of LigaSure™ versus conventional bipolar techniques on operating time and blood loss during laparoscopic salpingo-oophorectomy in a randomized controlled trial. In three teaching hospitals, 100 women undergoing a laparoscopic salpingo-oophorectomy were randomized for LigaSure or conventional bipolar instruments. Primary outcome was operating time (from initial skin incision to removal of the specimen). Secondary outcome measures were total operating time (from initial skin incision to skin closure), time to dissect the ovarian and infundibulopelvic ligaments, intraoperative blood loss, and subjective judgment of the instrument used. There were no differences in operating time and total operating time using LigaSure versus conventional bipolar instruments: 41.0 vs. 39.2 min (p = 0.78; 95 % CI = -10.9 to 14.5) and 54.6 vs. 58.6 min (p = 0.46; 95 % CI = -14.8 to 6.8), respectively. The mean blood loss using LigaSure versus conventional bipolar instruments was 38 vs. 33 mL (p = 0.73; 95 % CI = -22.7 to 32.2). Various subjective efficacy and instrument handling parameters of the two instruments varied among participating centers. There were no significant differences in operating time and blood loss with the use of LigaSure compared to conventional bipolar instruments during laparoscopic salpingo-oophorectomy, even after correction for potential confounders.


Immunomodulatory effect and safety of TNF-α RNAi mediated by oral yeast microcapsules in rheumatoid arthritis therapy.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that requires long-term treatment and monitoring. Inhibition of inflammatory gene expression by gene therapy is a significant breakthrough in RA treatment, but the lack of a safe and effective gene delivery system hinders its application. Since oral administration can significantly reduce wound infection caused by parenteral administration, it also has the advantages of high patient compliance and convenience. Therefore, oral administration may be the best option for the treatment of this chronic disease. In this study, we developed a novel oral drug system by delivering tumor necrosis factor-α (TNF-α) short hairpin RNA (shRNA) mediated by non-pathogenic yeast to evaluate its regulation of systemic immune inflammation and safety in RA. Non-pathogenic yeast can resist the destruction of the gastrointestinal acid-base environment and can be recognized by the intestinal macrophages and act on systemic inflammatory lesions. Oral administration of yeast-mediated TNF-α shRNA significantly reduced the expression of TNF-α predominant pro-inflammatory factors in intestinal macrophages and joint synovium, and up-regulated the expression of anti-inflammatory cytokine IL-10 and M2 macrophages, systematically regulating the inflammatory response. This yeast-mediated oral gene delivery system can not only significantly inhibit knee joint synovial inflammation, but also has no toxic effects on peripheral blood and major organs. Therefore, yeast-mediated oral delivery of TNF-α shRNA may be used as a novel gene therapy strategy to treat RA through immunomodulating the mononuclear phagocyte system from the intestine to the joint synovium, and ultimately regulating systemic and local immune inflammation, providing new ideas for the clinical treatment of RA.


Carbohydrate-deficient transferrin and alcohol use in medical examiner cases.
Carbohydrate-deficient transferrin (CDT) has been studied as an index of heavy alcohol use. The present study evaluates the utility of CDT as a marker for chronic alcohol use in medical examiner cases. Over a 5-month period, serum specimens were collected in consecutive deaths that were referred to the medical examiner's office (N = 25). Manner of death was accidental in nine cases, homicide/suicide for eight cases, and natural causes for seven cases. Fifteen of the 17 cases having alcohol abuse had positive CDT levels above threshold, indicating chronic use (sensitivity 88%). Eight cases had no evidence of alcohol abuse but three of these cases had CDT levels also above threshold (specificity 63%). There was no correlation between serum CDT levels and the time of death to blood collection for the total sample, indicating that CDT is stable postmortem for at least 36 h. CDT appears to have value as a marker of ante-mortem alcohol use prior to time of death in medical examiner cases.


Potential auto-driving threat: Universal rain-removal attack.
Severe weather conditions pose a significant challenge for computer vision algorithms in autonomous driving applications, particularly regarding robustness. Image rain-removal algorithms have emerged as a potential solution by leveraging the power of neural networks to restore rain-free backgrounds in images. However, existing research overlooks the vulnerability concerns in neural networks, which exposes a potential threat to the intelligent perception of autonomous vehicles in rainy conditions. This paper proposes a universal rain-removal attack (URA) that exploits the vulnerability of image rain-removal algorithms. By generating a non-additive spatial perturbation, URA significantly diminishes scene restoration similarity and image quality. The imperceptible and generic perturbation employed by URA makes it a crucial tool for vulnerability detection in image rain-removal algorithms and a potential real-world AI attack method. Experimental results demonstrate that URA can reduce scene repair capability by 39.5% and image generation quality by 26.4%, effectively targeting state-of-the-art rain-removal algorithms.


Melanoma-specific survival in patients with positive sentinel lymph nodes: Relevance of sentinel tumor burden.
The tumor burden within the sentinel lymph node (SLN) is not included in the 8th edition of the American Joint Committee of Cancer (AJCC) melanoma classification. Therefore, we analysed the prognostic relevance of the SLN tumor burden in the stage III subgroups. A total of 736 patients with melanoma with positive SLN and long-term follow-up (mean, 64.4 months; median, 59.0 months) were assessed. SLN tumor burden was evaluated by the maximum diameter of the largest deposit in all patients. By univariate Kaplan-Meier analyses, melanoma-specific survival (MSS) of patients in stage IIIA, IIIB and IIIC and lower sentinel tumor burden (cut-offs ≤0.5 mm and ≤1 mm) was significantly better than that in patients with higher sentinel tumor load (>0.5 mm and >1 mm). By multivariate analysis using the Cox model, the maximum diameter of the largest deposit (cut-off ≤0.5 mm versus >0.5 mm and cut-off ≤1 mm as continuous variables) represented an independent prognostic parameter for MSS in stage III patients. Cut-off of 0.5 mm showed a slightly higher area under the receiver operating characteristic curve (AUC = 0.617) when than the cut-off of 1 mm (AUC = 0.599). The prognosis of patients with stage III melanoma can be determined more precisely if the SLN tumor burden is considered, also within the existing AJCC subgroups. Thus, this parameter should be included in future classifications, and our study provides benchmarks in estimating prognosis and counselling patients with melanoma with positive sentinel nodes beyond the 8th AJCC Cancer Staging Manual. The optimal cut-off remains for SLN tumor burden remains to be determined, but our results suggest that a cut-off lower than 1 mm is preferable.


Users' Perceptions About Lower Extremity Orthotic Devices: A Systematic Review.
To systematically review perceptions from adults, children, and caregivers in scientific and open sources to determine how well lower extremity orthotic devices (LEODs) meet users' functional, expressive, aesthetic, and accessibility (FEA2) needs. Scientific source searches were conducted in the National Library of Medicine (PubMed/MEDLINE) and Web of Science; open source searches were conducted in Google Search Engine in April 2020. Inclusion criteria were reporting of users' perceptions about a LEOD, experimental or observational study design, including qualitative studies, and full text in English. Studies were excluded if the device only provided compression or perception data could not be extracted. One hundred seventy three scientific sources of 3440 screened were included (total of 1108 perceptions); 36 open sources of 150 screened were included (total of 508 perceptions). Users' perceptions were independently coded by 2 trained, reliable coders. Across both source types, there were more perceptions about functional needs, and perceptions were more likely to be positive related to functional than expressive, aesthetic, or accessibility needs. Perceptions about expression, aesthetics, and accessibility were more frequently reported and more negative in open vs scientific sources. Users' perceptions varied depending on users' diagnosis and device type. There is significant room for improvement in how LEODs meet users' FEA2 needs, even in the area of function, which is often the primary focus when designing rehabilitation devices. Satisfaction with LEODs may be improved by addressing users' unmet needs. Individuals often choose not to use prescribed LEODs even when LEODs improve their function. This systematic review identifies needs for LEODs that are most important to users and highlights how well existing LEODs address those needs. Attention to these needs in the design, prescription, and implementation of LEODs may increase device utilization.


Subsurface biogeochemical cycling of nitrogen in the actively serpentinizing Samail Ophiolite, Oman.
Nitrogen (N) is an essential element for life. N compounds such as ammonium ( NH 4 + ) may act as electron donors, while nitrate ( NO 3 - ) and nitrite ( NO 2 - ) may serve as electron acceptors to support energy metabolism. However, little is known regarding the availability and forms of N in subsurface ecosystems, particularly in serpentinite-hosted settings where hydrogen (H2) generated through water-rock reactions promotes habitable conditions for microbial life. Here, we analyzed N and oxygen (O) isotope composition to investigate the source, abundance, and cycling of N species within the Samail Ophiolite of Oman. The dominant dissolved N species was dependent on the fluid type, with Mg2+- HCO 3 - type fluids comprised mostly of NO 3 - , and Ca2+-OH- fluids comprised primarily of ammonia (NH3). We infer that fixed N is introduced to the serpentinite aquifer as NO 3 - . High concentrations of NO 3 - (>100 μM) with a relict meteoric oxygen isotopic composition (δ18O ~ 22‰, Δ17O ~ 6‰) were observed in shallow aquifer fluids, indicative of NO 3 - sourced from atmospheric deposition (rainwater NO 3 - : δ18O of 53.7‰, Δ17O of 16.8‰) mixed with NO 3 - produced in situ through nitrification (estimated endmember δ18O and Δ17O of ~0‰). Conversely, highly reacted hyperalkaline fluids had high concentrations of NH3 (>100 μM) with little NO 3 - detectable. We interpret that NH3 in hyperalkaline fluids is a product of NO 3 - reduction. The proportionality of the O and N isotope fractionation (18ε / 15ε) measured in Samail Ophiolite NO 3 - was close to unity (18ε / 15ε ~ 1), which is consistent with dissimilatory NO 3 - reduction with a membrane-bound reductase (NarG); however, abiotic reduction processes may also be occurring. The presence of genes commonly involved in N reduction processes (narG, napA, nrfA) in the metagenomes of biomass sourced from aquifer fluids supports potential biological involvement in the consumption of NO 3 - . Production of NH 4 + as the end-product of NO 3 - reduction via dissimilatory nitrate reduction to ammonium (DNRA) could retain N in the subsurface and fuel nitrification in the oxygenated near surface. Elevated bioavailable N in all sampled fluids indicates that N is not likely limiting as a nutrient in serpentinites of the Samail Ophiolite.


Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates.
A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities.


The specificity of antibody response in experimental and natural bovine paratuberculosis studied by crossed immunoelectrophoresis with intermediate gel.
The sonicate antigen (MPS) of a local strain (IVRI) of Mycobacterium paratuberculosis and a commercial lysate of Strain 18 were analysed using hyperimmune rabbit and calf antisera to MPS in crossed immunoelectrophoresis with intermediate gel (CIE-ig) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The rabbit antiserum was more potent than the calf antiserum and it precipitated 35 and 15 antigens, respectively, among MPS and lysate antigens. SDS-PAGE resolved 50 and 32 peptides among these antigens respectively, of which, 35 and 15 were precipitated by rabbit antiserum. A CIE-ig reference system, with 30 MPS antigens, was standardized and used to analyse antibody specificities among sera derived from animals experimentally and naturally infected with bovine paratuberculosis. Fourteen antigens of MPS were found to be reactive with these sera and among these, Antigens 2 and 5 were found to be serodominant; sonicate antigens of M. bovis BCG and M. avium did not contain these antigens. Both were high molecular weight (greater than 60 kDa) antigens which may be of serodiagnostic value.


The Wolfiporia cocos Genome and Transcriptome Shed Light on the Formation of Its Edible and Medicinal Sclerotium.
Wolfiporia cocos (F. A. Wolf) has been praised as a food delicacy and medicine for centuries in China. Here, we present the genome and transcriptome of the Chinese strain CGMCC5.78 of W. cocos. High-confidence functional prediction was made for 9277 genes among the 10,908 total predicted gene models in the W. cocos genome. Up to 2838 differentially expressed genes (DEGs) were identified to be related to sclerotial development by comparing the transcriptomes of mycelial and sclerotial tissues. These DEGs are involved in mating processes, differentiation of fruiting body tissues, and metabolic pathways. A number of genes encoding enzymes and regulatory factors related to polysaccharide and triterpenoid production were strikingly regulated. A potential triterpenoid gene cluster including the signature lanosterol synthase (LSS) gene and its modified components were annotated. In addition, five nonribosomal peptide synthase (NRPS)-like gene clusters, eight polyketide synthase (PKS) gene clusters, and 15 terpene gene clusters were discovered in the genome. The differential expression of the velevt family proteins, transcription factors, carbohydrate-active enzymes, and signaling components indicated their essential roles in the regulation of fungal development and secondary metabolism in W. cocos. These genomic and transcriptomic resources will be valuable for further investigations of the molecular mechanisms controlling sclerotial formation and for its improved medicinal applications.


Pericapsular nerve group block in hip arthroplasty: A prospective randomized trial.
This study aimed to evaluate the analgesic effect of the ultrasound-guided pericapsular nerve group (PENG) block in hip arthroplasty (HA) surgery. A prospective double-blinded, randomized study. Tertiary institutional clinical care. Fifty patients, more than 50 years old of both genders, were chosen according to the American Society of Anesthesiologists classification, with physical status I-III, and scheduled for unilateral HA surgeries. Patients were randomized to receive either a sham PENG block with 20 mL of normal saline (control group) or a PENG block with 20 mL of bupivacaine 0.25 percent (PENG group). From the onset of the first request for rescue opioid analgesia, preoperative pain scores before and after block (at rest and with a raised straight leg), the incidence of quadriceps weakness after the block, intraoperative fentanyl consumption, post-operative pain scores, and morphine consumption, besides the presence and frequency of adverse events, were recorded. The patients undergoing PENG block with bupivacaine had prolonged durations before the first analgesic request, lower perioperative pain scores, less intraoperative rescue fentanyl, and less post-operative morphine consumption than the control group, with nonsignificant motor weakness after the block and similar adverse events. The PENG block provided effective perioperative analgesia for HA with prolonged duration of analgesia, nonsignificant motor effects, reduced perioperative opioids consumption, and no major side effects.


Biodegradable implant application: Electrodeposition of HA/TiO2/ZrO2 coating onto Zn-composite substrates.
Zinc has currently emerged as a promising biodegradable metal due to its good biocompatible property and promising degradation behaviour. Additionally, inadequate mechanical strength and a lower cell viability value fall short of what is needed for biodegradable implants. In this work, we used the stir-casting process to create a biodegradable Zn-1Mg-1Cu-1HA (ZHA) and Zn-1Mg-1Cu-1ZrO2 (ZZR) composite onto which ceramics composite coating is done by electrodeposition technique to enhance the biocompatibility. The as-cast sample has uniformly distributed fine MgZn2 and CuZn2 phases in a α-Zn matrix, according to microstructural analysis. The mechanical test confirms that ZZR composite exhibited high tensile and compressive properties, including compressive yield strength of 369.562 MPa, a yield tensile strength of 88.725 MPa and ultimate tensile strength of 116.21 MPa. The result of potentiodynamic polarization test shows that the coated ZZR composite sample gives a corrosion rate value of 0.112 mm/year. From immersion tests, the degradation rate obtained a much lower value after immersing the sample in PBS solution for 55 days (0.067 mm/year). Moreover, an extract of coated ZZR composite shows good cell viability in comparison to the uncoated sample at a concentration of 25%, 50% and 75%. Also, the hemolysis percentage for coated ZZR sample is lower than the other prepared uncoated sample (3.072%) Overall, the result obtained proves that the coated ZZR composite sample can be expected as a capable material for implant application.


Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria.
Thiol-group oxidation of active and allosteric cysteines is a widespread regulatory posttranslational protein modification. Pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus, use regulatory cysteine oxidation to respond to and overcome reactive oxygen species (ROS) encountered in the host environment. To obtain a proteome-wide view of oxidation-sensitive cysteines in these two pathogens, we employed a competitive activity-based protein profiling approach to globally quantify hydrogen peroxide (H2O2) reactivity with cysteines across bacterial proteomes. We identified ∼200 proteins containing H2O2-sensitive cysteines, including metabolic enzymes, transcription factors, and uncharacterized proteins. Additional biochemical and genetic studies identified an oxidation-responsive cysteine in the master quorum-sensing regulator LasR and redox-regulated activities for acetaldehyde dehydrogenase ExaC, arginine deiminase ArcA, and glyceraldehyde 3-phosphate dehydrogenase. Taken together, our data indicate that pathogenic bacteria exhibit a complex, multilayered response to ROS that includes the rapid adaption of metabolic pathways to oxidative-stress challenge.


Transcranial Direct Current Stimulation Optimization - From Physics-Based Computer Simulations to High-Fidelity Head Phantom Fabrication and Measurements.
Transcranial direct current stimulation (tDCS) modulates neural networks. Computer simulations, while used to identify how currents behave within tissues of different conductivity properties, still need to be complemented by physical models. To better understand tDCS effects on biology-mimicking tissues by developing and testing the feasibility of a high-fidelity 3D head phantom model that has sensing capabilities at different compartmental levels. Models obtained from MRI images generated 3D printed molds. Agar phantoms were fabricated, and 18 monitoring electrodes were placed on specific phantom brain areas. When using rectangular electrodes, the measured and simulated voltages at the monitoring electrodes agreed reasonably well, except at excitation locations. The electric field distribution in different phantom layers appeared better confined with circular electrodes compared to rectangular electrodes. The high-fidelity 3D head model was found to be feasible and comparable with computer-based electrical simulations, with high correlation between simulated and measured brain voltages. This feasibility study supports testing to further assess the reliability of this model.


Chronic prenatal ethanol exposure alters the proportion of GABAergic neurons in layers II/III of the adult guinea pig somatosensory cortex.
Chronic prenatal ethanol exposure increases the expression of gamma-aminobutyric acid type A (GABA(A)) receptors in the adult guinea pig cerebral cortex. One possible explanation for this change in receptor number is the loss of GABAergic innervation and subsequent up-regulation of GABA(A) receptors. We tested this hypothesis by determining the relative proportion of glutamic acid decarboxylase (GAD) immunopositive cells in the cerebral cortex of adult guinea pig offspring that had received chronic daily exposure to ethanol (4 g/kg maternal body weight) throughout gestation. Chronic prenatal exposure to ethanol decreased the number of neurons that were GAD-immunopositive relative to the total number of cresyl-violet-stained neurons by approximately 30% in layers II/III of the adult guinea pig somatosensory cortex. No changes were observed in other cortical layers. These data suggest that chronic prenatal exposure to ethanol results in either a selective loss of GABAergic interneurons or failure to express GAD in layers II/III of the adult guinea pig somatosensory cortex.


A rapid and sensitive non-competitive avidin-biotin assay for lactoferrin.
We have developed an avidin-biotin assay for the detection of lactoferrin in human seminal plasma. We compared 5 modifications of this assay, and found the non-competitive avidin-biotin assay (NABA) to be the most sensitive. The detection limit of 3-step NABA was 0.2 or 0.1 ng lactoferrin/ml, depending whether avidin-biotin-peroxidase complex (ABC) or avidin-peroxidase was used. The intra-assay and inter-assay coefficients of variation for 3-step NABA were 6.2 and 8.5%, respectively. The lactoferrin levels of human seminal plasma samples measured by 3-step NABA and radioimmunoassay (RIA) showed good correlation (r = 0.96). The total performance time of 3-step NABA is flexible and the method can be modified for rapid (less than 1 h) or overnight assay according to need.


DFT study on the catalytic decomposition of hydrogen peroxide by iron complexes of nitrilotriacetate.
The Fenton system in the presence of nitrilotriacetate (NTA) ligand is studied by DFT approach. The calculations show that complexation of Fe(II) with NTA significantly facilitates the H2 O2 activation. The ferric-hydroperoxo intermediate NTAFe(III)OOH predominantly decays via the disproportionation into NTAFe(II)OH2 and NTAFe(IV)O involving the formation of a μ-1,2-hydroperoxo-bridged biferric intermediate. In this mechanism, the bridged hydroperoxo is reduced by hydroperoxo ligand rather than by Fe(III). On the one hand, the NTAFe(III)OOH is sluggish to undergo hydrogen abstraction; on the other hand, it is a good nucleophile that may perform aldehyde deformylation. The present calculations suggest that both ˙OH and Fe(IV)O are generated in the NTA-assisted Fenton system. However, the polycarboxylate ligand provides a favorable environment for H2 O2 to accumulate around iron ion through hydrogen bonding. This promotes the quenching of Fe(IV)O by H2 O2 , rationalizing why the Fe(IV)O species is hardly detected in the NTA-assisted Fenton system.


Introducing novel and comprehensive models for predicting recurrence in breast cancer using the group LASSO approach: are estimates of early and late recurrence different?
In here, we constructed personalized models for predicting breast cancer (BC) recurrence according to timing of recurrence (as early and late recurrence). An efficient algorithm called group LASSO was used for simultaneous variable selection and risk factor prediction in a logistic regression model. For recurrence < 5 years, age (OR 0.96, 95% CI = 0.95-0.97), number of pregnancies (OR 0.94, 95% CI = 0.89-0.99), family history of other cancers (OR 0.73, 95% CI = 0.60-0.89), hormone therapy (OR 0.76, 95% CI = 0.61-0.96), dissected lymph nodes (OR 0.98, 95% CI = 0.97-0.99), right-sided BC (OR 0.87, 95% CI = 0.77-0.99), diabetes (OR 0.77, 95% CI = 0.60-0.98), history of breast operations (OR 0.38, 95% CI = 0.17-0.88), smoking (OR 5.72, 95% CI = 2.11-15.55), history of breast disease (OR 3.32, 95% CI = 1.92-5.76), in situ component (OR 1.58, 95% CI = 1.35-1.84), tumor necrosis (OR 1.87, 95% CI = 1.57-2.22), sentinel lymph node biopsy (SLNB) (OR 2.90, 95% CI = 2.05-4.11) and SLNB+axillary node dissection (OR 3.50, 95% CI = 2.26-5.42), grade 3 (OR 1.79, 95% CI = 1.46-2.21), stage 2 (OR 2.71, 95% CI = 2.18-3.35), stages 3 and 4 (OR 5.01, 95% CI = 3.52-7.13), and mastectomy+radiotherapy (OR 2.97, 95% CI = 2.39-3.68) were predictors of recurrence < 5 years. Moreover, relative to mastectomy without radiotherapy (as reference for comparison), quadrantectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence < 5 years. (OR 17.58, 95% CI = 6.70-46.10 vs. OR: 2.50, 95% CI = 2-3.12). Accuracy, sensitivity, and specificity of the model were 82%, 75.6%, and 74.9%, respectively. For recurrence > 5 years, stage 2 cancer (OR 1.67, 95% CI = 1.31-2.14) and radiotherapy+mastectomy (OR 2.45, 95% CI = 1.81-3.32) were significant predictors; furthermore, relative to mastectomy without radiotherapy (as reference for comparison), quadranectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence > 5 years (OR 7.62, 95% CI = 1.52-38.15 vs. OR 1.75, 95% CI = 1.32-2.32). Accuracy, sensitivity, and specificity of the model were 71%, 78.8%, and 55.8%, respectively. For the first time, we constructed models for estimating recurrence based on timing of recurrence which are among the most applicable models with excellent accuracy (> 80%).


A computer-controlled system to perturb the ankle joint of freely standing cats trained to maintain a given force.
A computer-based system was developed to (1) train freely standing cats to match various target forces with the left hindlimb, (2) perturb the left ankle joint when the cat was maintaining a desired force and (3) compare reflex responses before and after decerebration. Cats quickly learned to stand unaided on 4 pedestals. During a training session, a range of target force windows was presented to the cat. A successful trial consisted of maintaining the force applied on the left rear pedestal within the target window for a preset time period. To assist the cat, a light was turned on whenever the force was within the target window. A food pellet reward was delivered by the computer after each successful trial. To test reflex responses, the position of the left hindlimb could be briefly perturbed by activating a servo-controlled printed motor configured to rotate the pedestal about the axis of the ankle joint. Perturbations that either flexed or extended the ankle joint were presented pseudo-randomly by the computer. This approach has been used to quantify the magnitude of muscle afferent volleys and the reflex EMG in ankle extensor muscles of normal and decerebrated cats, in response to similar mechanical perturbations. It has also been used to study dynamic features in the electroneurogram recorded from a cutaneous nerve by implanted nerve cuff electrodes, and the correlations among the electroneurogram, the vertical contact force applied on the pedestal and the force recorded from muscle tendons by implanted transducers. This approach may have general applications in the study of postural control, including the study of the discharge patterns of individual motor, sensory or spinal cord neurons in freely standing cats.


The nanotoxicity investigation of optical nanoparticles to cultured cells in vitro.
Optical nanoparticles (NPs) have the potential to provide new tools for diagnosis and treatment of human diseases, however, their nanotoxicity and biological characteristics are still unclear. Here, we prepared a series of typical NPs (including gold nanospheres, gold nanorods, silver nanopheres, silver triangular nanoplates and quantum dots) with different material and surface chemical modification for nanotoxicity test. Cell proliferation was investigated by SRB assay where the NPs were co-cultured with cancer cells. It was found that NPs' toxicity was highly correlated to different factors-material selection, physical size/surface area, shape, and surface chemical property, etc. This work has the potential to provide a uniform and systematic information when they are applied as probes in biological and medical fields.


Role of single prolonged stress in acquisition of alcohol conditioned place preference in rats.
Previous studies showed that exposure to certain types of stressors enhance the rewarding effects of many drugs of abuse, including alcohol; however, no systematic study has investigated the role of single prolonged stress (SPS) in acquisition of alcohol conditioned place preference (CPP). The purpose of this study was to examine whether SPS would facilitate the acquisition of alcohol CPP in rats. Male Sprague-Dawley rats were randomly assigned to either SPS exposure condition or no exposure condition. Freezing behavior and Elevated plus maze (EPM) were employed to evaluate PTSD-like symptoms induced by SPS. Further, using unbiased procedure, CPP conditioning was conducted with alcohol (2g/kg). SPS significantly enhanced freezing behavior of rats, decreased percentages (%) of both time spent and number of entry into the open arms, and facilitated the acquisition of alcohol CPP without inhibiting rats' activity. Our findings suggest that SPS plays an important role in alcohol dependence, and CPP paradigm with SPS may be useful for exploring the rewarding mechanism of alcohol with regard to the interaction between alcohol and post-traumatic stress disorder (PTSD).


Electronically phase separated nano-network in antiferromagnetic insulating LaMnO3/PrMnO3/CaMnO3 tricolor superlattice.
Strongly correlated materials often exhibit an electronic phase separation (EPS) phenomena whose domain pattern is random in nature. The ability to control the spatial arrangement of the electronic phases at microscopic scales is highly desirable for tailoring their macroscopic properties and/or designing novel electronic devices. Here we report the formation of EPS nanoscale network in a mono-atomically stacked LaMnO3/CaMnO3/PrMnO3 superlattice grown on SrTiO3 (STO) (001) substrate, which is known to have an antiferromagnetic (AFM) insulating ground state. The EPS nano-network is a consequence of an internal strain relaxation triggered by the structural domain formation of the underlying STO substrate at low temperatures. The same nanoscale network pattern can be reproduced upon temperature cycling allowing us to employ different local imaging techniques to directly compare the magnetic and transport state of a single EPS domain. Our results confirm the one-to-one correspondence between ferromagnetic (AFM) to metallic (insulating) state in manganite. It also represents a significant step in a paradigm shift from passively characterizing EPS in strongly correlated systems to actively engaging in its manipulation.


Neural activity pattern is not necessary for the development of adult ultrastructure in katydid (Neoconocephalus robustus) singing muscles.
The singing muscles of the katydid Neoconocephalus robustus develop adult ultrastructure late in the last nymphal instar and during the first few days of adult life. The ultrastructural changes during early adulthood were not affected by unilateral axotomy shortly after the adult molt. Both denervated and innervated muscles developed adult proportions of mitochondria, myofibril, and sarcoplasmic reticulum and transverse tubules.


Antithrombotic and thrombolytic activities of Agkisacutacin, a snake venom proteinase, in experimental models.
The antithrombotic and thrombolytic activities of Agkisacutacin (Agk), a component isolated from Agkistrodon acutus, were determined in vitro and in vivo. The models employed included Chandler's model, arterio-venous shunt model and pulmonary embolus model. The effects of Agkisacutacin on coagulation, plasma fibrinogen and platelet aggregation induced by collagen, adenosine diphosphate (ADP) and thrombin were also investigated. The results showed that Agkisacutacin can significantly inhibit thrombus formation in Chandler's and arterio-venous shunt models, and accelerate thrombolysis of pulmonary emboli in rats. The data suggested that Agkisacutacin possessed antithrombotic and thrombolytic activities. Agkisacutacin was also partial characterized.


Changes in Left Ventricular Mechanics After Sleeve Gastrectomy.
The aim of this study was to examine echocardiographic parameters of left ventricle (LV) mechanics in obese patients before and after sleeve gastrectomy (SG). Twenty-five obese individuals submitted to laparoscopic SG were enrolled in this study. Echocardiography was performed before and after the procedure, and left ventricle mechanics were evaluated by speckle tracking imaging. Before surgery, altered global longitudinal strain (GLS) values were present in 56% of the patients. In a mean follow-up of 3.6 ± 0.5 months after surgery, there was an increase in GLS values (from 17.4 ± 3.2 to 19.3 ± 2.7%, P = 0.01). There was an inverse correlation between the absolute values of GLS in the preoperative period and the variation in the GLS at follow-up (r = 0.577, P = 0.002). Measurements of global circumferential strain (GCS), global radial strain (GRS), and LV twist were normal preoperatively and did not change after surgery. Altered global longitudinal strain values were common in young obese patients. Sleeve gastrectomy increased global longitudinal strain even in the early postoperative phase without promoting changes in global radial strain, global circumferential strain, and left ventricle twist measurements.


Testing the photosynthetic bacterium Rhodobacter sphaeroides as heavy metal removal tool.
We present some preliminary results relevant to the ability of the purple non-sulphur bacterium Rhodobacter sphaeroides strain R26.1 to sequester heavy metals from contaminated growth media. The microorganism was chosen because of its significant tolerance to relatively high concentrations of the investigated ions Ni2+, Co2+, CrO4(2-), and MoO4(2-). In this paper the optimized conditions for the bacterial growth and the sample preparation used to infer the ability of the microorganism to cope with metal pollutants are presented. Elemental analysis has been performed by inductively coupled plasma atomic emission spectrometry previous mineralization of samples by a microwave system.


Epidermal growth factor modulates fetal thymocyte growth and differentiation.
In the present study, we used the fetal organ culture (FTOC) technique in order to study a putative effect of epidermal growth factor (EGF) on the thymus ontogeny. Functional EGF receptors and more recently the EGF molecule itself, respectively, on the membrane of epithelial components of thymic stroma and on a few thymocytes in adult thymus, had been reported in the literature. We could observe a dose-dependent decrease in cellularity and a progressive retention of thymocytes in the double-negative (CD4-/CD8-) stage of differentiation when exogenous EGF was added. Epidermal growth factor interfered with both fetal stroma growth and thymocyte development at a precise moment, that is, in the passage from double-negative to the double-positive (CD4+/CD8+) stage. After a 7-day FTOC in the presence of EGF, most cells recovered were Thy-1.2+, c-kit+, TSA1-/int, CD3-, and one of CD44high/CD25int, CD44-/CD25int, or CD44/CD25-. Some developed into gammadeltaTCR+ cells with a mature (CD3+) phenotype, but not into alphabetaTCR+ thymocytes. It seems that EGF addition makes the cultures "nonpermissible" for alphabetaTCR+ thymocyte generation. We report here the presence of a high Mr "EGF-like" molecule on the membrane of fetal thymocytes, which role in the observed effects is under investigation. Further biochemical characterization of this molecule is still required, because its presence was only evidenced on the basis of its antigenicity.


Localized fibrous mesothelioma of the liver. Report of a giant tumor studied by light and electron microscopy.
A benign localized mesothelioma weighing 3800 g was removed from the liver of a 27-year-old woman. The tumor was studied by light and electron microscopy, and immunohistochemically, and was found to be composed of fibroblastic and epithelial cells.


Insertion of self-expanding metal stents for malignant dysphagia: assessment of a simple endoscopic method.
To assess the efficacy, safety and long-term results of self-expanding metallic prostheses, placed using an entirely endoscopic method, for the relief of dysphagia in oesophageal carcinoma. A consecutive series of 50 patients (30 men, 20 women), aged 43-91 years (median, 75 years) underwent stent placement (Ultraflex Stent, Boston Scientific, Watertown, MA, USA) under general anaesthesia without fluoroscopic control. Stent placement was successful in all patients. Swallowing improved from dysphagia score 4, 3 or 2 to score 1 (or 0) in all patients available for long-term follow-up (excluding two patients who died, and two who had resection, in the immediate post-stenting period). There were two early deaths that were, or could have been, procedure-related and one early complication, in addition to technical problems in 6 cases, all early in the series. Seven patients required endoscopic laser treatment, on 13 occasions, subsequently for tumour in-growth or over-growth. Of the 46 patients with long-term stents in situ, 36 patients died with a median survival time of 4 months (range 10 days to 24 months). At the time of writing, 10 patients are still alive with a median survival of 4 months (range 1-11 months). Self-expanding metallic stents provide rapid, safe and effective relief of dysphagia. They can provide long-term palliation (> 1 year) with endoscopic laser treatment for recurrent in-growing/over-growing tumour. Fluoroscopic control is not necessary for the safe and accurate placement of such stents.


A minimal intron length but no specific internal sequence is required for splicing the large rabbit beta-globin intron.
We constructed rabbit beta-globin genes with deletions in the large intron, extending from the midpoint toward the 5' or 3' splice sites. Analysis of transcripts in transformed HeLa cells showed that six 5' proximal intron nucleotides allowed normal splicing. Correct splicing at the 3' splice site required 12 or more 3' proximal intron nucleotides; optimal efficiency required 24 nucleotides. Remarkably, a mini-intron comprising six 5' and 24 3' intron nucleotides gave no correctly spliced transcripts; extending the miniintron with polyoma or pBR322 fragments to 80 or more nucleotides restored normal splicing. Thus other than in yeast nuclear genes, no specific internal intron sequences appear to be needed but a minimal intron length is important.


Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia.
Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.


Cortical axons branch to multiple subcortical targets by interstitial axon budding: implications for target recognition and "waiting periods".
We are studying how axons branch in vivo. Individual cortical neurons send axons to both the spinal cord and the basilar pons. Here we show that the corticopontine projection develops by an interstitial budding of collaterals from parent axons rather than a reported mechanism of axon branching, growth cone bifurcation. This mechanism is used regardless of whether the parent axon's postpontine segment, which forms the corticospinal projection, is permanent (motor cortex) or transient (visual cortex). Budding occurs days after the parent axons grow spinally past the pons, accounting for the "waiting period" reported in this system in contrast to an alternative explanation that the growth cones pause outside of their target. Timing and location of pontine collateral budding vary with cortical origin of the parent axon and are correlated with the temporal ordering of axon arrival.


Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance.
Over the past decade, the non-steroidal antiestrogen tamoxifen has gained general acceptance for the palliative treatment of breast cancer. Although there has been much interest in the pharmacology of tamoxifen, our knowledge of its metabolism in laboratory animals and patients is incomplete and the precise mechanism of action within target tissue and breast tumor cells is unknown. This review briefly describes the pharmacology of tamoxifen in various laboratory species and patients. Several metabolites of tamoxifen are known and their relative potencies as estrogens and antiestrogens are compared with the parent compound. Apart from monohydroxytamoxifen, none of tamoxifen's metabolites are more potent antiestrogens, but a metabolite in the dog, Metabolite E, is fully estrogenic. Routine assays (tlc, HPLC, glc/ms) are available to detect tamoxifen, N-desmethyltamoxifen, monohydroxytamoxifen, and a newly identified metabolite, designated Metabolite Y, in biological fluids. Continuous therapy with tamoxifen (10 mg bid) produces steady-state levels (100-200 ng/ml serum) within 4 weeks. Levels of N-desmethyltamoxifen are often up to twice the levels achieved with tamoxifen, while levels of monohydroxytamoxifen and Metabolite Y are below 10 ng/ml. Although monohydroxytamoxifen has a high binding affinity for the estrogen receptor, the metabolic activation of tamoxifen is an advantage rather than a requirement for antiestrogenic activity. The action of tamoxifen in vivo is the net result of the individual actions of the parent compound and its metabolites competing for the occupation of receptors within target tissues and tumors.


Applications and Current Medico-Legal Challenges of Telemedicine in Ophthalmology.
The digital revolution is redesigning the healthcare model, and telemedicine offers a good example of the best cost-effectiveness ratio. The COVID-19 pandemic has catalysed the use of the telemedicine. The aim of this review is to describe and discuss the role and the main applications of telemedicine in the ophthalmic clinical practice as well as the related medico-legal aspects. 45 original articles and 5 reviews focused on this topic and published in English language from 1997 and 2021 were searched on the online databases of Pubmed, Scopus, Web of Sciences and Embase, by using the following key words: "telemedicine", "privacy", "ophthalmology", "COVID-19" and "informed consent". Telemedicine is able to guarantee patient care using information and communication technologies. Technology creates an opportunity to link doctors with the aim of assessing clinical cases and maintaining high standards of care while performing and saving time as well. Ophthalmology is one of the fields in which telemedicine is most commonly used for patient management. Telemedicine offers benefits to patients in terms of saving time and costs and avoiding physical contact; however, it is necessary to point out significant limitations such as the absence of physical examinations, the possibility of transmission failure and potential violations of privacy and confidentiality.


Relationship of word knowledge to word frequency in young adult deaf students.
This report describes research that has been undertaken to determine the relationship between word knowledge and word frequency (occurrence in print) in a deaf population. A matching test was designed and administered to 162 deaf students entering the National Technical Institute for the Deaf in the summer of 1976. The results of the study indicate that there exists a relationship between word frequency and word knowledge in a deaf population. The reliability and validity of the technique was tested and seems to provide adequate support for this approach to assessing the vocabulary level of deaf students.


Factors Associated with Food Delivery App use Among Young Adults.
Food delivery apps are popular among young adults and often used to purchase calorie-dense foods. Limited research exists on the use of food delivery apps among young adults. The purpose of this study was to describe food delivery app use among young adults and examine the correlates of food delivery app use. Data are from a panel of U.S. young adults aged 18-25 (n = 1,576) who completed an online survey between January-April 2022. Participants were 51.8% female and 39.3% identified as non-Hispanic white, 24.4% as Hispanic/Latinx, 29.6% as non-Hispanic Black, and 6.8% as another race/ethnicity. Poisson regression was used to examine the relationship between food delivery app use and age, race, ethnicity, sex, SES, food insecurity, living arrangement, financial responsibility, and full-time student status. Young adults used food delivery apps approximately twice a week. Participants who identified as non-Hispanic Black and Hispanic/Latinx used food delivery apps more frequently than participants who identified as white. Having higher perceived subjective social status, food insecurity, financial responsibility, and being a full-time student were significantly associated with using food delivery apps more frequently. Living with someone else was associated with using food delivery apps less frequently. This study provides a first step in understanding the characteristics of young adults who use food delivery apps. Given that food delivery apps are a new technology that can both increase access to unhealthy food options as well as healthy food options, further research is needed to better understand the types of food purchased through food delivery apps.


Client perspectives on the accessibility and quality of substance use treatment during the COVID-19 pandemic.
People who use drugs have been particularly vulnerable during the COVID-19 pandemic because of their unique social, harm reduction, and treatment needs. These unique needs and challenges have significant influence on the severity of their substance use, mental health symptomatology, willingness to engage in treatment, and adherence to treatment options. This has included immense challenges related to the dissemination of COVID-19 messaging and the need for harm reduction and treatment service entities to adopt new formats to continue operation. In-depth interview data were collected people who use drugs (N=24) residing in Oklahoma from November 2020 through February 2021 to assess perspectives on (1) their access to harm reduction, substance use prevention, and treatment programs during the COVID-19 pandemic, (2) the perceived quality of such services and programs during this time, and (3) the perceived availability of tailored COVID-19 information. Several factors emerged related to accessing and quality of substance use services during COVID-19, including poor accessibility (e.g., internet access), diminished quality (i.e., lack of social support), and lack of tailored COVID-19 prevention and treatment messaging. Upticks in COVID-19 cases and deaths are expected to continue as new SARS-CoV-2 variants are introduced. The present findings highlight the need for tailored COVID-19 messaging (e.g., minimizing the sharing of substance use supplies that can spread COVID-19, mask wearing, COVID-19 vaccination), which is responsive to unique needs of substance using populations. Similarly, as prevention and treatment programs are delivered online, efforts are necessary to ensure equitable access and enhanced quality of services.


Enzymes and biopolymers. The opportunity for the smart design of molecular delivery systems.
Enzymes exhibit a tremendous potential due to the catalytic activity in response to physiological conditions and specific microenvironments. Exploiting these properties in combination with the versatility of biopolymers, a fascinating field for the rational development of a new class of "smart" delivery systems for therapeutic molecules is proposed. Many strategies have been recently developed to produce matrices with the desirable properties of molecular release, and enzymes could be playing a relevant role in modify the chemical composition of the polymers, the porosity and surface area of the matrices and modulate the kinetic of controlled release. Enzyme based computational systems have appeared as a relevant complementary tool to design novel smart bioactive matrices for programmable drug delivery. The present review is reporting the recent advances and projections of smart biopolymeric matrices activated by enzymes for sustained release of therapeutic molecules, highlighting various applications in the area of advanced drug delivery.


Effect of Anti-Iduronate 2-Sulfatase Antibodies in Patients with Mucopolysaccharidosis Type II Treated with Enzyme Replacement Therapy.
To assess the relationship between anti-Iduronate 2-sulfatase (IDS) antibodies, IDS genotypes, phenotypes and their impact in patients with enzyme replacement therapy (ERT)-treated Mucopolysaccharidosis type II. Dutch patients treated with ERT were analyzed in this observational cohort study. Antibody titers were determined by enzyme-linked immunosorbent assay. Neutralizing effects were measured in fibroblasts. Pharmacokinetic analysis of ERT was combined with immunoprecipitation. Urinary glycosaminoglycans were measured using mass spectrometry and dimethylmethylene blue. Eight of 17 patients (47%) developed anti-IDS antibodies. Three patients with the severe, neuronopathic phenotype, two of whom did not express IDS protein, showed sustained antibodies for up to 10 years of ERT. Titers of 1:5120 or greater inhibited cellular IDS uptake and/or intracellular activity in vitro. In 1 patient who was neuronopathic with a titer of 1:20 480, pharmacokinetic analysis showed that all plasma recombinant IDS was antibody bound. This finding was not the case in 2 patients who were not neuronopathic with a titer of 1:1280 or less. Patients with sustained antibody titers showed increased urinary glycosaminoglycan levels compared with patients with nonsustained or no-low titers. Patients with the neuronopathic form and lack of IDS protein expression were most at risk to develop sustained anti-IDS antibody titers, which inhibited IDS uptake and/or activity in vitro, and the efficacy of ERT in patients by lowering urinary glycosaminoglycan levels.


A visual disorder producing highly selective deletion of recurring letters.
A case of unusually selective deletion of recurring letters is described. The disorder was primarily visual, spelling being unaffected. There was no evidence of neglect. Reading was fluent and rapid (not letter-by-letter), though words often appeared as a series of resolving fragments. Selective deletions were entirely confined to adjacent letters, excluding explanation in terms of repetition blindness (Kaniwisher, 1991). Mixing case and font, or increasing inter-letter distance, did not alter rate of recurring letter deletion, provided the task required some form of perceptual grouping. The final 2 experiments establish the pre-lexical nature of the deficit; they show deletion of recurring symbols, for example, when copying Navon-style global forms constructed from same or different Greek letters. This visual deficit is explained using the neural network model developed by Rolls and Deco (2002).


Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival.
Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described. The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n = 85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR. Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P < 0.001) and ERα (P = 0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P < 0.0001), PR (P < 0.0001) and ERβ (P < 0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P = 0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P < 0.0001, P < 0.0001, respectively). Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.


An enzymatic method for the assay of serum argininosuccinate lyase.
A rapid enzymatic method was developed for the assay of serum argininosuccinate lyase (ASAL: EC 184.108.40.206) which is a useful marker enzyme for diagnosis of parenchymal liver diseases. Fumarate, liberated from argininosuccinate in the lyase-mediated reaction, was converted to pyruvate via L-malate by the actions of fumarase and malic enzyme in the presence of NADP+. The NADPH formed was then oxidized with a diaphorase-resazurin system to give a highly fluorescent resorufin. All the enzymatic reactions proceeded continuously in 0.1 M Tris-HCl buffer (pH 7.5) and allowed direct assay of ASAL in serum by monitoring the increase in the fluorescence intensity due to resorufin. The method is rapid and sensitive; only 50 microliter of serum is required. This method was used to detect increases in the activities in sera from patients with liver diseases.


Isolation of L-form variants after antibiotic treatment in Staphylococcus aureus bovine mastitis.
An unstable L-form of Staphylococcus aureus was identified in milk samples from 3 quarters of 2 cows after treatment with cloxacillin. Milk samples incubated on standard 5% blood agar plates were culture-negative for 7 to 30 days after treatment, but S aureus was reisolated in 80% of 66 samples by additional culturing on enriched L-form media when incubated in 10% CO2 at 37 C. The organism was identified at various phases of reversion of L-form agar and was confirmed on transfer to blood agar plates.


Ca2(+)-dependent mobility shift of parvalbumin in one- and two-dimensional gel-electrophoresis.
Under Ca2(+)-loaded conditions parvalbumin migrates in one- and two-dimensional gel-systems as a double-band or -spot whereas in Ca2(+)-free condition it appears as one band or spot. Parvalbumin (PV), a member of the family of calcium-binding proteins [1], was first described in 1934 [2] and occurs in fast-contracting muscles and in subpopulations of neurons in vertebrates and humans [3,4,5]. The physical characteristics of molecular weight (Mv 12 KD), isoelectric point (pI 4.9) and Ca2(+)-binding properties are established (PV binds 2 Ca2+ per molecule) [5,6]. Physiological roles discussed for PV range from trigger- to buffer-protein of intracellular Ca2(+)-ions [7]. In this paper we report an as yet not described mobility shift of PV in gel-electrophoresis after manipulation of the Ca2+ concentration, which may have implications for its physiological function.


Purification and characterization of native type XIV collagen.
A new molecule, type XIV collagen, with domains homologous to type IX and XII collagens has been recently discovered in pepsin extracts of fetal bovine tissues (Dublet, B., and van der Rest, M. (1991) J. Biol. Chem. 266, 6853-6858). In the present study, we describe the purification and the characterization of the intact native form of this newly discovered collagen. By using only two chromatographic steps we were able to obtain pure type XIV collagen. Furthermore, minor modifications of the protocol allowed us to perform the simultaneous large scale purification of type XII and type XIV collagens from the same tissue. Intact type XIV collagen migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as two bands of 220 and 290 kDa (reducing conditions). After collagenase treatment, a single band of 190 kDa is observed, which represents the large non-collagenous domain of the molecule (NC3). Rotary shadowing electron micrographs of intact type XIV collagen show a cross-shaped structure formed by a thin tail attached through a central globule to three identical "fingers." These properties are similar to those previously described for intact chicken type XII collagen (Dublet, B., Oh, S., Sugrue, S. P., Gordon, M. K., Gerecke, D. R., Olsen, B. R., and van der Rest, M. (1989) J. Biol. Chem. 264, 13150-13156), but the two molecules are different gene products and have charge and glycosylation differences. Finally, we show that the three chains of purified type XIV collagen have an apparent molecular mass of approximately 220 kDa and are not cross-linked to each other by bonds other than disulfide bridges. The same observation was made for type XII collagen. In both cases, the 290-kDa migrating band in SDS-PAGE is due to incomplete denaturation in electrophoresis sample buffer in the absence of urea.


Hourly monitoring of circulating CD34+ cells to optimize timing of autologous apheresis in pediatric patients.
In order to increase the CD34+ cell yield in children undergoing autologous stem cell transplantation, the optimum time of apheresis after G-CSF administration has still to be found. We prospectively studied the mobilization of CD34+ cells and white blood cells in the peripheral blood (PB) of 20 pediatric patients before leukapheresis. The monitoring schedule covered 12 h, with blood samples taken before and at 2, 4, 5, 6, 7, 8, 10 and 12 h after G-CSF administration when 10 CD34+ cells/mul were reached. CD34+ cells were measured by flow cytometric analysis both in the single- and dual-platform setting. Two different patterns of mobilization (POM) emerged: 12 patients showed an increase in CD34+ cells in PB during the first 4 h after G-CSF (POM I), while eight patients had an initial decrease of CD34+ cells. However, all patients together showed a significant increase of CD34+ cells about 10 h after G-CSF administration. Further studies with more patients, using an enhanced monitoring schedule will be required to refine the results.


Genetic predisposition to impaired metabolism of the branched chain amino acids, dietary intakes, and risk of type 2 diabetes.
Circulating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters. We estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c. Dietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 μmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals. Our study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility.


Cellulose acetate - essential oil nanocapsules with antimicrobial activity for biomedical applications.
This study aimed to obtain bioactive nanosystems by combining cellulose acetate with three selected essential oils (EOs) to create spherical nanocapsules (NCs) using the solvent/anti-solvent technique. The biological activity of the obtained NCs was promoted by the use of some antimicrobial EOs: Peppermint, Cinnamon and lemongrass which were grafted on the cellulose acetate molecules. Due to their chemistry, such as long hydrocarbon tails and heads with functional groups these EOs were playing also the role of surfactant-like substance facilitating the formation of NCs. A dispersion of NCs was obtained in water and various spectroscopy techniques used to examine their size, morphology and chemistry. Dynamic light scattering calculate the size of the NCs whereas scanning electron microscopy showed their morphology. Fluorescent microscopy and Raman spectroscopy proved the attachment of the EOs in the cellulose acetate molecules. The antimicrobial activity of the obtained nanomaterials was tested against four microbial strains (bacteria: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and a yeast strain of Candida albicans). The obtained results demonstrated that such NCs can be used in a variety of applications including medical, pharmaceutical recipients and in household products for treating or preventing microbial colonization and biofilm development.


The effect of saline loading on uranium-induced acute renal failure in rats.
Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion.


Treatment Outcomes of Childhood Medulloblastoma with the SIOP/UKCCSG PNET-3 Protocol.
To retrospectively compare the overall and event-free survival rates of patients with standard and high risk medulloblastoma who received postoperative radiotherapy (RT) followed by maintenance chemotherapy. The study included 48 patients with medulloblastoma who were treated and followed-up between 2005 and 2021. Patients were classified according to the Chang classification because no molecular analysis was done. Immediately after surgery all patients received postoperative RT followed by eight cycles of chemotherapy (SIOP/UKCCSG PNET-3 protocol); if thrombocytopenia developed, carboplatin was replaced by cisplatin to avoid treatment delay. The clinical characteristics, risk categories and treatment outcomes of all patients were analyzed. The mean age of the 48 patients (26 males, 22 females) at diagnosis was 7.27±4.21 y. The median start time of RT after surgery was 37 (range 19-80) d. The median follow-up was 56 (3-216) mo. The 5-year event-free survival was 61.2±10% in the high-risk group and 82.5±11.5% in the standard-risk group. The 5-year overall survival was 73.2±7.1%; it was 61.2±10% and 92.9±6.9% for high- and standard-risk patients, respectively (p = 0.026). The outcomes of patients who were started on the modified SIOP/UKCCSG PNET-3 chemotherapy protocol, in which RT was begun as soon as possible after surgery, were comparable to those of current treatment protocols. Although a definitive conclusion is difficult, given the limited number of patients in the present study, authors suggest that their treatment protocol is a viable option for centers with limited facilities (such as an inability to perform molecular analysis).


Illumination levels in commonly used ophthalmic devices.
Pupil diameter is a key parameter for corneal and multifocal intraocular lens surgery. Many devices are dedicated to measure the pupil size, but do not specify the illumination during capture. The aim of this study was to present illumination levels in routinely used ophthalmic devices which present pupil sizes. To obtain measurements, the lux meter was placed in the chin rest in the corneal plane and the room was completely dimmed. Ten measurements were taken for each device. The illumination levels for white and red Placido disk corneal topographers were 1253.1 ± 0.2 and 329.0 ± 0.2 lux, respectively (both photopic conditions). Scheimpflug corneal tomography should be considered as a mesopic measurement (14.5 ± 0.1 lux). Optical coherence tomography and autorefractometry are scotopic measurements (0.4-0.6 lux). We postulate that producers should provide illumination levels of their devices measuring pupil size. Moreover, when mentioning a pupil size, one should consider presenting to what lighting conditions it refers to.


Magnetic resonance vessel wall imaging predicts morphological deterioration in unruptured intracranial artery dissection.
The mechanism involved in progression of unruptured intracranial artery dissection (IAD) is poorly understood. We investigated the relationship between contrast enhancement of dissecting lesions on magnetic resonance vessel wall imaging (MR-VWI) and unruptured IAD progression on the hypothesis that this finding might predict its instability. A total of 49 unruptured IADs were investigated retrospectively. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast medium, and the dissecting lesion/pituitary stalk contrast enhancement ratio (CRstalk) was calculated. Unruptured IAD progression was defined as morphological deterioration; progressive dilatation or stenosis. The relations between unruptured IAD progression and potential risk factors were statistically investigated. Morphological deterioration was demonstrated in eleven of 49 unruptured IADs (22 %). The CRstalk value and male predominance was significantly higher in progressed IADs than stable ones (1.0 vs. 0.65; p = 0.0035, 82% vs 37%; p= 0.015, respectively). On stepwise multivariable logistic regression analysis, the CRstalk value was independently associated with unruptured IAD progression with odds ratio of 102.5 (95% CI, 2.59-4059, P=0.0013). The optimal cutoff value of CRstalk to estimate IADs with progression was 0.87 (sensitivity, 0.82; specificity, 0.74). Multimodalic images showed contrast enhancement on VWI corresponded to residual stagnant flow in dissecting lesions. Quantitative analysis of contrast enhancement on VWI could predict instability of unruptured IADs. Contrast enhancement in dissecting lesions would be a clue to understand the mechanism of unruptured IAD progression.


Risk-Appropriate Care to Improve Practice and Birth Outcomes.
Identification and referral of women with high-risk pregnancies to hospitals better equipped and staffed to provide care for them have been important steps to improve birth outcomes. Based on recent recommendations from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine to provide regionalized maternal care for pregnant women at high risk and reduce rates of maternal morbidity and mortality, health care organizations and providers have refocused their attention to women's well-being rather than solely on the well-being of the fetus or newborn. Opportunities to improve practice and birth outcomes exist through the implementation of a more standardized and integrated system of risk-appropriate care.


Determination of the antioxidant capacity in blood.
A vast amount of scientific research is directed towards the beneficial effects of antioxidants on health. For this reason, several assays have been developed to determine the total antioxidant capacity of blood. In this study two procedures based on the use of the green-blue 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS(*+)) were compared. In the first (commercially available) procedure, ABTS(*+) was generated in the presence of the blood sample. In the second procedure, referred to as the decolorization assay, antioxidants react with preformed ABTS(*+). It was found that the first procedure leads to greater underestimation of the actual antioxidant capacity and is more prone to artifacts than the second procedure. Therefore, only the latter procedure was evaluated in detail and it appeared that (i) plasma is preferred over serum, (ii) the high background produced by albumin can be circumvented by deproteination, (iii) samples can be stored at -80 degrees C for 12 months, and (iv) the assay has high precision. Due to poor linearity, the procedure has to be standardized to allow sample comparison. The decolorization assay is a reliable and robust assay that can be applied routinely to predict the antioxidant capacity of blood.


A tumor immunotherapy technique based on modulation of the idiotype anti-idiotype network.
In this communication I propose a technique for manipulating the idiotype anti-idiotype network with the aim of enhancing the immune response to tumors. The theoretical basis for this technique follows from Jerne's network theory of the immune system. By tolerizing the host to immunoglobulin bearing idiotypes directed against tumor associated antigens it should be possible to dampen the expected anti-idiotype response to these idiotypes. A reduced anti-idiotype response should result in an increased idiotype response and thus a greater anti-tumor immune response.