Obligate and facultative anaerobic bacteria in targeted cancer therapy: Current strategies and clinical applications.
Traditional methods for cancer therapy, including radiotherapy, chemotherapy, and immunotherapy are characterized by inherent limitations. Bacteria-mediated tumor therapy is becoming a promising approach in cancer treatment due to the ability of obligate or facultative anaerobic microorganisms to penetrate and proliferate in hypoxic regions of tumors. It is widely known that anaerobic bacteria cause the regression of tumors and inhibition of metastasis through a variety of mechanisms, including toxin production, anaerobic lifestyle and synergy with anti-cancer drugs. These features have the potential to be used as a supplement to conventional cancer treatment. To the best of our knowledge, no reports have been published regarding the most common tumor-targeting bacterial agents with special consideration of obligate anaerobes (such as Clostridium sp., Bifidobacterium sp.) and facultative anaerobes (including Salmonella sp., Listeria monocytogenes, Lactobacillus sp., Escherichia coli, Corynebacterium diphtheriae and Pseudomonas sp). In this review, we summarize the latest literature on the role of these bacteria in cancer treatment.


Linking the activity measure for post acute care and the quality of life outcomes in neurological disorders.
To use item response theory (IRT) methods to link physical functioning items in the Activity Measure for Post Acute Care (AM-PAC) and the Quality of Life Outcomes in Neurological Disorders (Neuro-QOL). Secondary data analysis of the physical functioning items of AM-PAC and Neuro-QOL. We used a nonequivalent group design with 36 core items common to both instruments and a test characteristic curve transformation method for linking AM-PAC and Neuro-QOL scores. Linking was conducted so that both raw and scaled AM-PAC and Neuro-QOL scores (mean ± SD converted-logit scores, 50 ± 10) could be compared. AM-PAC items were administered to rehabilitation patients in post-acute care (PAC) settings. Neuro-QOL items were administered to a community sample of adults through the Internet. PAC patients (N=1041) for the AM-PAC sample and community-dwelling adults (N=549) for the Neuro-QOL sample. Not applicable. Mobility (N=25) and activity of daily living (ADL) items (N=11) common to both instruments were included in analysis. Neuro-QOL items were linked to the AM-PAC scale by using the generalized partial credit model. Mobility and ADL subscale scores from the 2 instruments were calibrated to the AM-PAC metric. An IRT-based linking method placed AM-PAC and Neuro-QOL mobility and ADL scores on a common metric. This linking allowed estimation of AM-PAC mobility and ADL subscale scores based on Neuro-QOL mobility and ADL subscale scores and vice versa. The accuracy of these results should be validated in a future sample in which participants respond to both instruments.


Role of carbohydrate modification in weight management among obese children: a randomized clinical trial.
To compare the effectiveness and safety of carbohydrate (CHO)-modified diets with a standard portion-controlled (PC) diet in obese children. Obese children (n=102) aged 7-12 years were randomly assigned to a 3-month intervention of a low-CHO (LC), reduced glycemic load (RGL), or standard PC diet, along with weekly dietary counseling and biweekly group exercise. Anthropometry, dietary adherence, and clinical measures were evaluated at baseline and 3, 6, and 12 months. Analyses applied intention-to-treat longitudinal mixed models. Eighty-five children (83%) completed the 12-month assessment. Daily caloric intake decreased from baseline to all time points for all diet groups (P<.0001), although LC diet adherence was persistently lower (P<.0002). At 3 months, body mass index z score was lower in all diet groups (LC, -0.27 ± 0.04; RGL, -0.20 ± 0.04; PC, -0.21 ± 0.04; P<.0001) and was maintained at 6 months, with similar results for waist circumference and percent body fat. At 12 months, participants in all diet groups had lower body mass index z scores than at baseline (LC, -0.21 ± 0.04; RGL, -0.28 ± 0.04; PC, -0.31 ± 0.04; P<.0001), and lower percent body fat, but no reductions in waist circumference were maintained. All diets demonstrated some improved clinical measures. Diets with modified CHO intake were as effective as a PC diet for weight management in obese children. However, the lower adherence to the LC diet suggests that this regimen is more difficult for children to follow, particularly in the long term.


Systematic review of the complications of plate fixation of clavicle fractures.
The number of displaced midshaft clavicle fractures treated surgically is increasing and plate fixation is often the treatment modality of choice. The study quality and scientific levels of evidence at which possible complications of this treatment are presented vary greatly in literature. The purpose of this systematic review is to assess the prevalence of complications concerning plate fixation of dislocated midshaft clavicle fractures. A computer-based search was carried out using EMBASE and PUBMED/MEDLINE. Studies included for review reported complications after plate fixation alone or in comparison to either treatment with intramedullary pin fixation and/or nonoperative treatment. Two quality assessment tools were used to assess the methodological quality of the studies. Included studies were ranked according to their levels of evidence. After study selection and reading of the full texts, 11 studies were eligible for final quality assessment. Nonunion and malunion rates were less than 10% in all analysed studies but one. The vast majority of complications seem to be implant related, with irritation or failure of the plate being consistently reported on in almost every study, on average ranging from 9 to 64%. The quantity of relevant high evidence studies is low. With low nonunion and malunion rates, plate fixation can be a safe treatment option for acute dislocated midshaft clavicle fractures, but complications related to the implant material requiring a second operation are frequent. Future prospective trials are needed to analyse the influence of various plate types and plate position on implant-related complications.


Spontaneous rupture of the kidney secondary to polyarteritis nodosa.
Spontaneous rupture of the kidney occurs rarely. Among the known causes polyarteritis nodosa is uncommon with less than 50 cases reported. Diagnosis is difficult to make with certainty. Our case concerns a 38-year-old man whose symptoms originally simulated acute renal colic. Nephrectomy was done. A brief review of the pertinent literature, diagnosis and management is presented.


Plasma adiponectin concentration in early pregnancy and subsequent risk of hypertensive disorders.
Adiponectin is an exclusively adipose tissue-derived protein. Low plasma adiponectin levels have been found in hypertensive men. Our objective was to evaluate whether low first-trimester plasma adiponectin values were predictive of hypertensive disorders later in pregnancy. A nested case-control study was carried out on a cohort of 1,842 pregnant women who participated in the first-trimester Down syndrome screening program; 34 developed preeclampsia and 48 gestational hypertension. A control group of 82 nonhypertensive uneventful pregnancies was selected. Plasma adiponectin was determined using an enzyme-linked immunosorbent assay (ELISA). Adiponectin median concentrations in the group which subsequently became hypertensive were significantly lower than those in the control group (7.6 versus 13.0 microg/mL) (P < .001). When the 2 hypertensive subgroups were considered, the plasma adiponectin median value in the preeclampsia group was significantly lower than that in the gestational hypertension group (6.6 versus 9.3 microg/mL) (P = .01). Regression analysis showed an inverse correlation between plasma adiponectin concentrations and maternal age, gestational age, body mass index, systolic blood pressure, and proteinuria. Approximately 34% of hypertensive pregnancies, compared with 7% of controls (P < .001), had plasma adiponectin concentrations less than 6.4 microg/mL (mean value of lower quartile of distribution among control patients). After adjusting for maternal age, all these women experienced a 6.6-fold (95% confidence interval 2.5-17.8) increased risk of pregnancy hypertension, compared with those women who had higher concentrations. Our findings suggest a strong association between hypoadiponectinemia and the risk of hypertensive disorders in pregnancy, especially with preeclampsia.


Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is characterized by menstrual dysfunction and hyperandrogenism in the absence of other known causes. While the pathogenesis of PCOS remains elusive and is likely to involve abnormalities in several systems, there has long been an association of abnormal gonadotropin secretion with this disorder. In recent studies we have determined that 94% of women meeting the broad criteria for PCOS have an increased LH/FSH ratio. Several lines of evidence suggest that the mechanisms underlying the increased LH/FSH ratio in PCOS include an increased frequency of GnRH secretion. Decreased sensitivity to progesterone negative feedback on the GnRH pulse generator may play a role in this neuroendocrine defect. Additional factors which may contribute to the low to normal FSH levels in the face of increased LH include chronic mild estrogen increases and possibly inhibin. In addition to these effects on the differential control of FSH, there is increased pituitary sensitivity of LH secretion to GnRH. Both estrogen and androgens have been proposed as candidates mediating these effects. Superimposed on these underlying abnormalities in gonadotropin secretion is a marked inhibitory effect of obesity on LH secretion which may be mediated at either a pituitary or hypothalamic level.


OPA1 and PARL keep a lid on apoptosis.
A change in the shape of mitochondrial cristae must take place to attain rapid and complete release of cytochrome c during apoptosis. In this issue of Cell, Cipolat et al. and Frezza et al. (2006) show that a rhomboid intramembrane protease PARL and a dynamin-related protein OPA1 are critical regulators of cristae remodeling.


A novel indole-diterpenoid, JBIR-03 with anti-MRSA activity from Dichotomomyces cejpii var. cejpii NBRC 103559.
A new indole-diterpene, JBIR-03 (1), was isolated from the fungus Dichotomomyces cejpii var. cejpii NBRC 103559 and its structure was determined based on the spectroscopic data. 1 exhibited anti-MRSA (methicillin-resistant Staphylococcus aureus) activity and antifungal activity against apple Valsa canker-causing fungus, Valsa ceratosperma, while it exhibited no toxicity towards human cancer cells.


[Extract berberine hydrochloride by aqueous two-phase system].
To study the aqueous two-phase system which could be used for extraction of berberine hydrochloride. Three aqueous two-phase systems were used for extraction experiment firstly, the best one was chosen from that, and then the single factor experiment and orthogonal experiment were carried out. 10 mL 95% ethanol with 10 mL 2.2 mol/L ammonium sulfate could make a aqueous two-phase system, added 600 mg berberine hydrochloride whose purity was 53.22% into it, regulated its pH to 4, then the system was put into water-bath heater (70 degrees C) for 30 min, the extraction rate could reach 99.29%; Collected the extraction liquid, dried it under 40 degrees C, the purity of berberine hydrochloride was 88.43%. This system is a suitable aqueous two-phase system for extraction of berberine hydrochloride.


Serological differentiation between Echinococcus granulosus and E. multilocularis infections in man.
An enzyme-linked immunosorbent assay (ELISA) was adapted for the serological differential diagnosis of cystic or alveolar echinococcosis in man caused by Echinococcus granulosus or E. multilocularis respectively. By affinity chromatography using rabbit anti hydatid fluid IgG coupled covalently to CNBr-Sepharose 4B a protein fraction (Em 1) containing shared antigens of both parasites could be isolated from an extract of E. multilocularis metacestode tissue. From the same source another antigen fraction (Em 2) with a high degree of specificity for E. multilocularis was prepared by immunosorption. Antigen Em 1 was equally sensitive for the detection of antibodies against E. granulosus and E. multilocularis, whereas antigen fraction Em 2 appeared to be more specific for E. multilocularis. A correct serological differential diagnosis was achieved in 95% of 57 confirmed cases of human cystic or alveolar echinococcosis by the simultaneous use of both antigen fractions in the ELISA and by comparison of their reactivities.


Prevention of aggregation after refolding by balanced stabilization-destabilization: production of the Arabidopsis thaliana protein APG8a (At4g21980) for NMR structure determination.
The gene coding for APG8a (At4g21980), a protein from Arabidopsis thaliana, is involved in the autophagy process. The protein is an interesting candidate for structure determination by NMR spectroscopy. Toward this end, APG8a fused to an N-terminal His-tag has been expressed in Escherichia coli under a T7 expression system, refolded in vitro, and kept soluble by slight destabilization. The expressed protein appeared in both the soluble and the insoluble fractions. The whole-cell lysate was denatured by the addition of guanidinium chloride. The protein was immobilized on nickel-agarose resin and refolded by stepwise decrement of the denaturant. The elution buffer was 20 mM sodium phosphate, pH 7.0, with 1% glycerol, 0.5 M urea, 300 mM NaCl, and 1 M imidazole. After the removal of imidazole by ultrafiltration, the His-tag was cleaved with biotinylated thrombin. The protein product was kept in 20 mM sodium phosphate, pH 7.0, with 1% glycerol, 0.5 M urea, and 300 mM NaCl. The protein was found to aggregate extensively over time if any one of the three ingredients (sodium chloride, urea, or glycerol) was omitted. The yield of the protein was around 20 mg/L Luria-Bertani culture medium. The (1)H-(15)N NMR correlation spectrum of (15)N-labeled APG8a showed the characteristic signature of a folded protein; thus, the solutes appear to have no deleterious effect on the sample. These solution conditions kept the protein soluble and unaggregated for at least 2 days (enough time for NMR data collection). This approach of balanced stabilization-destabilization may offer a general approach for structural investigations of proteins that tend to aggregate.


Do sarcomere length, collagen content, pH, intramuscular fat and desmin degradation explain variation in the tenderness of three ovine muscles?
The longissimus (n=118) (LL), semimembranosus (n=104) (SM) and biceps femoris (n=134) (BF) muscles were collected from lamb and sheep carcases and aged for 5days (LL and SM) and 14days (BF) to study the impact of muscle characteristics on tenderness as assessed by shear force (SF) and sensory evaluation. The impact of gender, animal age, collagen content, sarcomere length (SL), desmin degradation, ultimate pH and intramuscular fat (IMF) on tenderness was examined. The main factors which influenced SF of the LL were IMF, SL and desmin degradation, but for sensory tenderness, IMF, ultimate pH and gender were the main factors. The SF and sensory tenderness of the SM was best predicted by the degree of desmin degradation. For the BF soluble collagen and animal age both influenced SF. Different factors affect tenderness across muscles and not one prediction model applied across all muscles equally well.


A mercury(II) ion sensor device based on an organic field effect transistor with an extended-gate modified by dipicolylamine.
Herein, we report an organic field effect transistor (OFET) with an extended-gate modified by an artificial receptor for the detection of mercury(II) ions (Hg(2+)) in water. The sensor device is easy to fabricate, reusable, disposable, and portable. Thus OFET sensors could be applied for low-cost on-site detection of Hg(2+).


Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes.
Interleukin-6 (IL-6) is a potent stimulator of the hepatic synthesis of acute-phase proteins. 125I-labelled IL-6 disappeared from the blood of rats with an overall half-time of about 1.5 min; 41% of the injected tracer dose was recovered in the liver by 15 min. The clearance was biphasic. The simultaneous injection of tracer and an excess of unlabelled IL-6 eliminated the initial rapid phase, and reduced the hepatic uptake to 14%. Light microscopic autoradiography showed 5% of the grains over non-hepatocytes, and 80% over hepatocytes, accumulating in areas around the bile canaliculi. Thereafter, degradation products accumulated in the bile. At 4 degrees C, isolated rat hepatocytes bound IL-6 with an apparent Kd of 39 pmol l-1 to a uniform class of 4500 receptors per cell with an apparent molar mass of 115-120 kg mol-1. The HepG2 human hepatocellular cell line bound IL-6 with an apparent Kd of 21 pmol l-1 to a uniform class of 1200 receptors per cell with an apparent molar mass of 155-160 kg mol-1. At 37 degrees C, both cell types endocytosed the bound ligand slowly, and degradation products appeared in the medium after a relatively long lag period (40 min in hepatocytes and 1 h in HepG2 cells).


Medullary sponge kidney and hyperparathyroidism.
Medullary sponge kidney (MSK), parathyroid adenoma, renal cell carcinoma, and renal-leak hypercalciuria coincided in 1 female patient. Renal-leak hypercalciuria was not corrected by removal of a parathyroid adenoma. Since the patient had renal tubular acidosis (RTA), alkali treatment was conducted and resulted in the correction of hypercalciuria. Renal cell carcinoma eventually developed and MSK was confirmed histologically. This case suggests that MSK and primary hyperparathyroidism occurred independently.


Genetic analysis of dog rabies viruses circulating in Bangkok.
The genetic diversity of the rabies virus glycoprotein (G) gene isolated from individual rabid dogs (inter-hosts) and within a single infected dog (intra-host) has been analyzed in an effort to better understand selective pressures and population shifts among rabies viruses circulating in Bangkok. Comparison of individual master sequences among inter-hosts revealed that the dog virus isolates circulating in Bangkok were phylogenetically closely related. The ectodomain of the glycoprotein was highly conserved among the virus isolates. Furthermore, the genetic diversity of the G gene within an intra-host was assessed by comparing the cloned sequences in the virus population. The comparisons revealed that rabies virus circulating in an intra-host consisted of closely related heterogenous populations with minor substitutions at nucleotide (0.19%) and amino acid levels.


Liver tumour MRI: what do we need for lesion characterization?
Hepatic lesions constitute a daily challenge to radiology in clinical settings, and non-invasive methods are valuable in the characterization of these liver tumours. We undertook our investigation to assess the lesion characterization potential of MRI by evaluating several unenhanced MR sequences and the dynamic gadolinium (Gd)-enhanced technique. A total of 116 focal liver lesions in 116 patients were included in our retrospective study, and histological verification was available for 107 lesions. Nine haemangiomas had a follow-up of 2 years. The 1.5-T MR system was used. T1- and T2-weighted sequences and dynamic Gd-enhanced studies were evaluated by two individual readers as separate sequences and also collectively. Lesions were classified into benign or malignant, and a specific diagnosis was proposed. The McNemar test was used in statistical analysis, and interobserver variation was measured using kappa statistics. Lesion classification into benign and malignant tumours (by evaluating all images in concert) was assessed in 83% and 89% of cases by readers 1 and 2, respectively. From single sequences, best lesion classification was achieved with Gd-enhanced T1 by both readers. The difference in classification was statistically significant when all sequences were evaluated in comparison with any single sequence alone (P = 0.02). Specific diagnosis was correctly determined using all sequences together in 60% and 71% of cases by readers 1 and 2, respectively. For individual sequences, correct diagnosis was most frequently proposed with a Gd-enhanced T1-weighted sequence by both readers (59% and 65% for readers 1 and 2, respectively). Multisequential MRI using Gd-enhanced imaging performs extremely well in liver lesion classification, and with moderate ability to determine a specific diagnosis.


Influence of product placement in children's movies on children's snack choices.
Media exposure affects health, including obesity risk. Children's movies often contain food placements-frequently unhealthy foods. However, it is not known if these cues influence children's food choices or consumption after viewing. We explored whether children's snack choices or consumption differs based on: 1) recent exposure to movies with high versus low product placement of unhealthy foods; and 2) children's weight status. Children ages 9-11 were assigned to watch a high ("Alvin and the Chipmunks," n = 54) or low ("Stuart Little," n = 60) product-placement movie. After viewing, participants selected a snack choice from each of five categories, several of which were specifically featured in "Alvin." Uneaten snacks from each participant were weighed upon completion. Snack choice and amount consumed by movie were compared by t-tests, and differences in snack choices by movie were tested with logistic regression. Participants consumed an average of 800.8 kcal; mean kcal eaten did not vary by movie watched. Participants who watched the high product-placement movie had 3.1 times the odds (95% CI 1.3-7.2) of choosing cheese balls (most featured snack) compared to participants who watched the low product-placement movie. Children who were overweight or obese consumed a mean of 857 kcal (95% CI: 789-925) compared to 783 kcal (95% CI: 742-823, p = 0.09) for children who were underweight or healthy weight. Children's weight status did not significantly affect their choice of snack. Branding and obesogenic messaging in children's movies influenced some choices that children made about snack foods immediately following viewing, especially food with greatest exposure time in the film, but did not affect total calories consumed. Future studies should examine how the accumulation of these messages affects children's long-term food choices.


Localized deep hyperthermia increases the traffic of lymphocytes through peripheral lymph nodes of sheep in vivo.
The production of localized deep hyperthermia by the radio frequency wave magnetic-loop induction method has been utilized to study the effects of deep hyperthermia on lymphocyte traffic in sheep in vivo. Deep hyperthermia has been applied both to primary peripheral lymph node drainage areas alone (popliteal and prefemoral) and directly over the study lymph node (popliteal). Deep tissue core temperatures were monitored in all studies and the findings were correlated with alterations in the levels of lymphocyte outputs into study node efferent lymph and the volume of efferent lymph flow. In all of 32 studies, there was a prompt and sharp increase in the output of lymphocytes into efferent lymph at 40-43 degrees C. Efferent lymph flow also was increased promptly but to a lesser degree than the output of lymphocytes. The two were not closely correlated. High deep temperature in the nodal area (45 degrees C) appeared to cause delayed nodal malfunction, which depressed lymphocyte output but did not affect lymph flow. Localized deep hyperthermia is an effective and noninvasive means for the local increase of lymphocyte traffic and lymph flow and may prove to be a useful means for the evaluation of the immunological consequences of altering both deep tissue temperature and lymphocyte traffic.


Managing COVID-19-positive Solid Organ Transplant Recipients in the Community: What a Community Healthcare Provider Needs to Know.
The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation. We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020-April 30, 2020. Patients were followed from time of testing to May 31, 2020. One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts. COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.


Comprehensive serologic profile and specificity of maternal and neonatal cord blood SARS-CoV-2 antibodies.
Initial studies on COVID-19 in pregnancy have demonstrated a range of neutralizing activity, but little has been published on the full profile of SARS CoV-2 related antibodies in maternal and cordblood. This study aimed to describe the profile and specificity of maternal and neonatal cord blood antibody profiles in response to SARS-CoV-2 virus exposure. This was a prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020 to February 2021. The primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in patients with COVID-19 history. Serologic profile was assessed with a multiplex platform. Antigens used were hemagglutinin trimer influenza A (Hong Kong H3); spike trimers for SARS-CoV-2, SARS-CoV-1, Middle East respiratory syndrome coronavirus, and betacoronaviruses HKU-1 and OC43; and spike N-terminal domain, spike receptor-binding domain, and nucleocapsid protein (full length) for SARS-CoV-2. Here, 112 maternal samples and 101 maternal and cord blood pairs were analyzed. Of note, 37 patients had a known history of COVID-19 (positive polymerase chain reaction test) during pregnancy. Of 36 patients, 16 (44%) were diagnosed with COVID-19 within 7 days of delivery. Moreover, 15 of the remaining 76 patients (20%) without a known diagnosis had positive maternal serology. For those with a history of COVID-19, we identified robust immunoglobulin G response in maternal blood to CoV-2 nucleocapsid, spike (full length), and spike (receptor-binding domain) antigens with more modest responses to the spike (N-terminal domain) antigen. In contrast, the maternal blood immunoglobulin M response seemed more specific to spike (full length) epitopes than nucleocapsid, spike (receptor-binding domain), or spike (N-terminal domain) epitopes. There were significantly higher maternal and cord blood immunoglobulin G responses not only to CoV-2 spike (127.1-fold; standard deviation, 2.0; P<.00001) but also to CoV-1 spike (21.1-fold higher; standard deviation, 1.8; P<.00001) and Middle East respiratory syndrome spike (6.9-fold higher; standard deviation, 2.5; P<.00001). In contrast, maternal immunoglobulin M responses were more specific to CoV-2 spike (15.8-fold; standard deviation, 2.1; P<.00001) but less specific to CoV-1 (2.5-fold higher; standard deviation, 0.71; P<.00001) and no significant difference for Middle East respiratory syndrome. Maternal and cord blood immunoglobulin G antibodies were highly correlated for both spike and nucleocapsid (R2=0.96 and 0.94, respectively). Placental transfer was efficient, with robust nucleocapsid and spike responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. Immunoglobulin G antibodies were cross-reactive with related CoV-1 and Middle East respiratory syndrome spike epitopes, whereas immunoglobulin M antibodies, which cannot cross the placenta to provide neonatal passive immunity, were more SARS-CoV-2 specific. Neonatal cord blood may have significantly different fine specificity than maternal blood, despite the high efficiency of immunoglobulin G transfer.


Effects of OSA treatment on BP in patients with resistant hypertension: a randomized trial.
OSA is extremely common among patients with resistant hypertension (HTN). However, the impact of the treatment of OSA with CPAP on BP in patients with resistant HTN is not well established. In the current study, 40 patients with confirmed resistant HTN and moderate to severe OSA confirmed by full polysomnography were randomized to medical therapy or to medical treatment plus CPAP for 6 months. Patients were evaluated at study baseline and after 6 months by 24-h ambulatory BP monitoring (ABPM). Thirty-five patients (77% men; age, 56 ± 1 years; BMI, median 32 kg/m² [25%-75%, 28-39 kg/m²]; apnea-hypopnea index, 29 events/h [24-48 events/h]; Epworth Sleepiness Scale, 10 ± 1; systolic/diastolic office BP, 162 ± 4/97 ± 2 mm Hg; taking four [four to five] antihypertensive drugs) completed the study. CPAP was used for 6:01 ± 0:20 h/night (3:42-7:44 h/night). Compared with the control group, awake systolic/diastolic ABPM decreased significantly in the CPAP group (Δ: +3.1 ± 3.3 /+2.1 ± 2.7 mm Hg vs -6.5 ± 3.3/-4.5 ± 1.9 mm Hg, respectively, P < .05). Interestingly, the BP changes were observed only while patients were awake, but not during nocturnal ABPM (Δ: +2.8 ± 4.5/+1.8 ± 3.5 mm Hg vs +1.6 ± 3.5/+0.8 ± 2.9 mm Hg, P = NS). The treatment of OSA with CPAP significantly reduces daytime BP in patients with resistant HTN. Therefore, our study reinforces the importance of recognizing and treating OSA in patients with resistant HTN. ClinicalTrials.gov; No.: NCT00812695; URL: www.clinicaltrials.gov.


Influence of the Ixodes ricinus tick blood-feeding on the antigen-specific antibody response in vivo.
The blood meal of hard ticks such as Ixodes ricinus lasts several days. This is made possible by tick salivary factors that inhibit inflammation, haemostasis and the host immune response. We assessed the latter on a model of immune response in vivo. A significant reduction of specific IgM and IgG levels was observed in BALB/c mice infested 5 days before injection with bovine serum albumin (BSA) and QuilA but not in mice infested 5 days after the immunization. This effect was not observed in mock-infested mice and could not be attributed to the use of anesthetics. The antibody response was not merely delayed and the Th(1)/Th(2) balance appeared not altered. T-dependent zones and germinal centers in lymph nodes draining the tick bite site showed no apparent morphological alterations or shift in T cell subpopulations. However, the spleens of tick-infested mice had also an enlarged red pulp, indicating an increased extramedullary haematopoietic activity.


Coronary Sinus Flow Is Reduced and Recovered With Time in Viral Myocarditis Mimicking Acute Coronary Syndrome: A Transthoracic Doppler Echocardiographic Study.
The clinical presentation of myocarditis often mimics acute coronary syndrome. Coronary sinus flow has been used for detection of the presence of myocardial ischemia. Whether myocarditis is associated with changes in coronary sinus flow remains unknown. The aim of this study was to assess coronary sinus flow at the onset and follow-up of myocarditis mimicking acute coronary syndrome using transthoracic Doppler echocardiography (TTE). Sixty-four patients with clinically diagnosed viral myocarditis mimicking acute coronary syndrome underwent TTE on days 3, 7, 30, 90, 180, and 360 after onset. Coronary sinus flow was compared among different points in time. Compared to healthy participants, all patients with myocarditis had a larger cardiac size, reduced cardiac function, and electrocardiographic and myocardial enzyme abnormalities on days 3 and 7 days (P< .01; P< .05). They later had gradual restoration to normal levels. On days 3 and 7, the coronary sinus flow in patients with myocarditis was extremely lower than that in healthy participants (about one-tenth), although coronary angiography revealed unobstructed arteries. On days 30, 90, 180, and 360, the coronary sinus flow had been increasing; however, it was still far less than that in healthy participants (P < .01). Coronary sinus flow depicted by TTE is reduced but recovers with time in viral myocarditis mimicking acute coronary syndrome, which is a useful indicator in the follow-up of this type of myocarditis.


At the Intersections: Examining Trends in Experiences of Violence, Mental Health Status, and Suicidal Risk Behaviors Among US High School Students Using Intersectionality, National Youth Risk Behavior Survey, 2015-2019.
Surveillance data are used for public health action, but the practice of analyzing data by single demographic characteristics may produce findings that reflect abstract categories rather than a person's lived experience. Intersectionality is a theoretical framework that advocates for individuals to be recognized as the whole of their identity and within context of power structures. Using the national Youth Risk Behavior Survey 2015-2019, we examined 5-year trends in experiencing violence, poor mental health, and suicidal risk behavior among US high school students using intersections of race/ethnicity and sex. We used SUDAAN to calculate prevalence estimates and logistic regression models to assess for linear trends while accounting for the weighting and complex survey design. Among all students in aggregate, experiencing dating violence decreased while being threatened with a weapon at school and feeling persistently sad or hopeless increased over time; however, these trends did not apply to most students when stratified by identity. The one near-universal experience was that students in aggregate and almost all identities had an increased trend of skipping school because they felt unsafe there. By focusing on identities defined by two main drivers of health disparities-race/ethnicity and sex-we found that changes in risk behaviors did not occur equally among students and that prevalence estimates were highest among Black males, Black females, and Hispanic females. We outlined the power structures that frame the current educational environment. Patterns of health disparities can be highlighted by analyzing surveillance data through an intersectional lens.


Upper limit of the time scale for diffusion and chain collapse in chymotrypsin inhibitor 2.
The rates of folding of wild-type chymotrypsin inhibitor 2 (CI2) (t1/2 = 12 ms) and of faster (t1/2 = 2 ms) and slower (t1/2 = 350 ms) folding mutants are accelerated in parallel by increasing concentrations of sucrose, despite the increases in viscosity. At a viscosity 26 times that of water, the folding rate constant of wild-type CI2 is accelerated four-fold (t1/2 = 2.7 ms). From this, we can estimate that the diffusional chain collapse in CI2 occurs in less than 100 micros in water, and is not rate-determining in folding.


Pharmacokinetics of carboplatin after intraperitoneal administration.
The pharmacokinetics of carboplatin, ultrafilterable platinum, and total platinum after intraperitoneal (i.p.) administration were studied in peritoneal fluid, plasma, red blood cells (RBCs), and urine during a phase-I trial in patients with minimal, residual ovarian cancer. Samples were collected from 7 patients who had received carboplatin (200-500 mg/m2) in 21 dialysis fluid. The fluid was withdrawn after a 4-h dwell. Platinum concentrations were measured by flameless atomic absorption spectrometry, and intact carboplatin was determined by HPLC with electrochemical detection. Peak concentrations of carboplatin in plasma were obtained 2 h after the end of instillation. The mean ratio of peak concentrations of carboplatin in instilled fluid and plasma was 24 +/- 11. The peritoneal clearance of carboplatin was 8 +/- 3 ml/min, which was 12 times less than the plasma clearance (93 +/- 32 ml/min). Due to this clearance ratio, the AUCs for the peritoneal cavity were about 10 times higher than those for plasma. On average, 34% +/- 14% of the dose was still present in the instillation fluid that had been withdrawn after a dwell time of 4 h. In plasma, the mean value of AUC/Dnet (Dnet = Dose - amount recovered from the peritoneal cavity) after i.p. administration was comparable with that of AUC/D after i.v. administration. This means that unrecovered carboplatin (66%) was completely absorbed from the peritoneal cavity. It may be expected from this bioavailability that the maximum tolerated dose (MTD) of i.p.-administered carboplatin with a 4-h dwell is around 1.5 times higher than that after i.v. administration. Overall pharmacokinetic parameters of carboplatin and platinum in plasma were comparable after i.p. and i.v. administration.


Physiologic changes and functional ability in the older patient: a challenge for the creative ET nurse.
In summary, older patients undergoing ostomy surgery require individual assessment of their functional abilities related to self-care. When deficits are identified it is the ET nurse who must respond with a creative, innovative approach that will assist the patient towards self-care, independence, and recovery.


Evaluation of middle ear and hearing status of ankylosing spondylitis patients with wideband tympanometry and pure tone audiometry tests.
The aim of this study was to evaluate the middle and inner ear function and hearing status of Ankylosing spondylitis (AS) patients. One hundred twenty-four ears of 62 patients with AS and 90 ears (control group) of 45 healthy subjects were included in the study. The hearing levels of the participants were assessed with pure tone and high-frequency audiometry at the octave frequency between 250 and 16,000 Hz. The absorbance rates and resonance frequencies of middle ear were measured with the wideband tympanometry (WBT) test. AS group was divided into subgroups based on the disease activity, duration of follow-up, medications used for AS, and the subgroups were compared according to hearing status and absorbance and resonance frequencies of middle ears. A statistically significant difference was found between the AS and control groups in terms of air and bone conduction thresholds at frequencies of 250, 500, 1000, 2000, and 4000 Hz and the mean PTA1, PTA2, and PTA3 values (p < 0.05). In contrast, no statistically significant difference was observed between two groups in terms of high-frequency thresholds (8000-16,000 Hz). Although the middle ear resonance frequency obtained from the WBT test was higher in the AS group compared to the control group, no significant difference was observed (p > 0.05). The severity of disease adversely affected the hearing threshold at 250, and 500 Hz for air conduction, at 500 Hz for bone conduction threshold, and at PTA1 (p < 0.05). The duration and severity of disease did not affect absorbance values of WBT (p > 0.05). To our knowledge, this is the first study to demonstrate the effects of AS patients on the middle ear function with WBT and to report middle ear absorbance values and resonance frequency changes in AS patients. The higher resonance frequency values found by WBT in AS patients may be due to the stiffness that develops as a result of middle ear involvement. According to pure tone and high-frequency audiometry findings, it has been seen that AS leads to SNHL especially at low frequencies.


Creating statewide tobacco control programs after passage of a tobacco tax: executive summary.
The tobacco control leaders of four states that have successfully passed tobacco tax ballot initiatives (California, Massachusetts, Arizona, and Oregon) were brought together to this conference to discuss what happens after the passage of such an initiative, how to defend tobacco control funds against diversion for other purposes by a state's legislature, and how to use the revenues maximally to reduce the health and economic toll taken by tobacco use. At the conference, the attendees from each state presented reports that will undoubtedly be useful to other states seeking to pass their own tobacco tax legislation or initiatives.


Catheter-less Cohen transtrigonal ureteric reimplantation.
To review the profile and outcome of patients in whom it was elected not to insert a bladder catheter as part of the management of Cohen transtrigonal ureteric reimplantation surgery. Between April 2000 and April 2001, 37 patients underwent ureteric reimplantation by the senior author, using the Cohen transtrigonal technique. The use of the catheter-less protocol began after the blockage of a suprapubic catheter soon after surgery; the catheter was removed with no adverse event. Subsequently, 27 of those undergoing ureteric reimplantation were selected not to have a bladder catheter. Later in the study a greater proportion of patients had no catheter inserted, as confidence with the catheter-less technique increased. Caudal anaesthetic, oral analgesia and a single dose of intravesical bupivacaine were used for pain relief. The children were monitored closely after surgery and a urethral catheter inserted in the one patient who had not voided after 6 h. The patients generally tolerated the lack of a bladder catheter well. Of the 27 patients who did not have a catheter inserted at surgery, one required catheterization (a girl with bilateral duplex systems and large ureteroceles). Two children stayed in hospital for 2 days after surgery, one was discharged on the day of surgery, and the remainder went home on oral analgesia on the first day after surgery. Since starting the catheter-less approach, 10 patients have had a suprapubic catheter because they had more complex surgery, were older or because the approach had not developed sufficiently at the time of surgery. Intravesical ureteric reimplantation is not only safe when omitting a bladder catheter but, if used selectively, there appears to be a significant decrease in the hospital stay and discomfort after surgery.


Popliteal Skin Lesion due to Wear Disease in Total Knee Arthroplasty: A Case Report.
An 87-year-old woman presented with a popliteal skin lesion due to polyethylene wear 13 years following a left total knee arthroplasty. Excisional biopsy through a posterior approach was performed. Histology showed inflammation with granulomas and birefringent foreign body particles in the skin. Cultures remained negative, and revision knee arthroplasty was performed. A popliteal skin lesion due to polyethylene wear disease in total knee arthroplasty has not previously been described. Patients with an atypical inflammation of the skin with an underlying joint implant should be referred to an orthopaedic surgeon, and dermal biopsies should be checked for birefringent material. Level V.


Postpartum screening for diabetes among Medicaid-eligible South Carolina women with gestational diabetes.
To examine the rate of timely postpartum screening for diabetes among Medicaid-eligible women with gestational diabetes mellitus (GDM). We examined a retrospective cohort of Medicaid women with a live birth between 2004 and 2007. Women with singleton live births at greater than 28 weeks gestation were included in the cohort and their screening receipt tracked. Only the first qualifying pregnancy within the observation period was assessed. Birth certificate records were linked with hospital discharge data, outpatient prenatal care claims to identify women with GDM (n = 6,239). Medicaid postpartum claims for these women were examined to determine receipt of postpartum screening for diabetes within 5 to 13 weeks. Women with any indication of a dedicated plasma glucose test identified by CPT codes 82947, 82950, 82951, and 82952 during this time period were considered to meet the definition of screening. Approximately 3.4% of women identified as having GDM were screened for diabetes postpartum. Adjusted analysis found women not attending the postpartum visit (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.91) and women receiving inadequate prenatal care (OR, 0.57; 95% CI, 0.34-0.95) were less likely to receive postpartum screening for diabetes. Conversely, women 20 to 34 years of age (OR, 1.79; 95% CI, 1.21-2.66) and women who were obese (OR, 2.28; 95% CI, 1.56-3.32) were more likely to be screened. Medicaid is a primary source of insurance for many women; however, for most coverage ends at 60 days postpartum, leaving a narrow window of opportunity for postpartum screening. Extended periods of coverage may be beneficial in ensuring the opportunity to receive adequate postpartum care, including screening for diabetes.


Correction: Tracking intramolecular energy redistribution dynamics in aryl halides: the effect of halide mass.
[This corrects the article DOI: 10.1039/C8RA04979C.].


The accuracy of blood pressure measured by arterial line and non-invasive cuff in critically ill children.
The accuracy of arterial lines (AL) using the flush test or stopcock test has not been described in children, nor has the difference between invasive arterial blood pressure (IABP) versus non-invasive cuff (NIBP) blood pressure. After ethics approval and consent, we performed the flush test and stopcock test on AL (to determine over damping, under damping, and optimal damping), and determined the difference (NIBP-IABP) in systolic, diastolic, and mean blood pressure (ΔSBP, ΔDBP, and ΔMAP). The primary outcome was incidence (95 % CI) of optimally damped AL. Predictors of ΔBP (effect size (95 % CI)) were determined using multiple linear regression. There were 147 AL tests in 100 enrolled patients with mean age 44.7 (SD 56) months, weight 16.8 (SD 18.3) kg, male 59 %, postoperative-cardiovascular 52 %, peripheral-AL 78 %, inotropes 29 %, vasodilators 15 %, and ventilated 73 %. The flush test performed in 66 patients (45 %) showed optimal damping in 30 (46 %; 95 % CI 34, 57 %), over damping in 25 (38 %) and under damping in 11 patients (17 %). The stopcock test was over-damped in 128/146 patients (88 %), with the same damping as the flush test in 24/64 (38 %). In optimally damped (flush test) AL, ΔSBP, ΔDBP, and ΔMAP were 0.8 (SD 12.2), -5.2 (SD 8.7), and -4.9 (7.6) respectively. A second set of AL tests was done 2 h later on the same day in 62 patients; AL damping often changed (10/28 flush tests) and ΔBPs correlated poorly (r = 0.31-0.55). Predictors (effect size) of ΔDBP were vasodilator infusion (15.6 (2.9 to 28.3); p = 0.016) and optimal damping (-7.2 (-12.2 to 2.2); p = 0.005); and of ΔMAP were vasodilator infusion (10.0 (-0.3 to 20.4); p = 0.057) and optimal damping (-4.0 (-8 to 0.1); p = 0.058). There were no independent predictors of damping category (n = 66 flush tests). Optimally damped AL occur in half of critically ill children, and this is not predictable. There is much variability in ∆BP between NIBP and the gold standard IABP, and this varies even in the same patient on the same day, and is not easily predictable. In critically ill children, NIBP may not be accurate enough to guide management, and more attention to ensuring the AL is optimally damped is needed.


Photonic synaptic transistors with new electron trapping layer for high performance and ultra-low power consumption.
Photonic synaptic transistors are being investigated for their potential applications in neuromorphic computing and artificial vision systems. Recently, a method for establishing a synaptic effect by preventing the recombination of electron-hole pairs by forming an energy barrier with a double-layer consisting of a channel and a light absorption layer has shown effective results. We report a triple-layer device created by coating a novel electron-trapping layer between the light-absorption layer and the gate-insulating layer. Compared to the conventional double-layer photonic synaptic structure, our triple-layer device significantly reduces the recombination rate, resulting in improved performance in terms of the output photocurrent and memory characteristics. Furthermore, our photonic synaptic transistor possesses excellent synaptic properties, such as paired-pulse facilitation (PPF), short-term potentiation (STP), and long-term potentiation (LTP), and demonstrates a good response to a low operating voltage of - 0.1 mV. The low power consumption experiment shows a very low energy consumption of 0.01375 fJ per spike. These findings suggest a way to improve the performance of future neuromorphic devices and artificial vision systems.


Soft sensors for on-line biomass measurements.
One of the difficulties encountered in control and optimisation of bioprocesses is the lack of reliable on-line sensors for their key state variables. This paper investigates the suitability of using on-line recurrent neural networks to predict biomass concentrations. Input variables of the proposed recurrent neural network are feed rate, liquid volume and dissolved oxygen. Experimental results revealed that the proposed neural network is able to predict biomass concentrations with an accuracy of +/-11%.


Effects of acid hydrolysis and mechanical polishing on surface residual stresses of low-fusing dental ceramics.
Cracks may arise in a ceramic restorative material over time, resulting in sudden fractures at stresses well below the yield stress. This study evaluated by means of indentation technique the effects of acid hydrolysis and mechanical polishing on the surface residual stresses of low-fusing ceramic materials. A total of 64 ceramic bars were formed to produce 4 groups of 16 bars each for 4 ceramic materials (Duceram-LFC Dentin, Duceram-LFC Enamel, Finesse Dentin, and Finesse Enamel). Four surface-treatment groups (n=4) were then formed for each of the 4 materials. The 4 surface treatments were control (autoglaze), hydrolysis, glaze/polish, and polish/glaze. A Vickers indenter contacted the Duceram-LFC specimens with a 5-N load and the Finesse specimens with a 3-N load for 10 seconds. Scanning electron microscope (SEM) was used to study surface texture before and after hydrolysis and polishing. Differences in mean crack lengths were analyzed with 1-way analysis of variance and least significant difference test (alpha=.05.) SEM showed obvious surface flaws as a result of hydrolysis on Duceram-LFC Enamel and Dentin specimens. However, statistical analysis of the resulting crack lengths revealed no significant differences between values for the control groups (58.16 +/- 3.88) (53.53 +/- 2.67) and hydrolysis groups (57.11 +/- 4.09) (54.54 +/- 3.15) for Enamel (P=.081) and Dentin (P=.093) respectively. When comparing polished groups and nonpolished groups, the mean crack lengths were significantly shorter for polished specimens of Duceram-LFC Enamel (53.76 +/- 3.17), Finesse Enamel (40.56 +/- 3.31), and Finesse Dentin (39.76 +/- 3.81) porcelains compared with their control groups (58.16 +/- 3.88) (43.54 +/- 4.12) (41.19 +/- 3.47), respectively (P<.0001). The mean crack lengths were significantly longer for polished specimens of Duceram-LFC Dentin (59.16 +/- 3.52) porcelain compared with the control group (53.53 +/- 2.67) (P<.0001). Within the limitations of this study, hydrolysis did not improve surface residual stresses of Duceram-LFC and Finesse ceramic materials. Mechanical polishing improved surface residual stresses of all materials tested, except Duceram-LFC Dentin porcelain.


Temporomandibular disorders in association with scuba diving.
To determine the prevalence of temporomandibular disorders (TMD) in scuba divers and to identify the risk factors for the development of pain in the stomatognathic system before and after diving by the use of a questionnaire. : Retrospective cohort study based on questionnaires. A total of 296 active divers, aged 18 to 65 years, participating in scuba diving meetings in Heidelberg, Germany. Each diver answered a questionnaire containing 29 questions, predominantly on symptoms of TMD. The data collected from the divers were calculated by the use of logistic regression tests. Risk factors for the development of TMD were evaluated. Clenching seemed to be the greatest risk factor for pain while holding the mouthpiece and for pain in the masticatory muscle system after diving. Limited mouth opening and clenching were responsible for the development of pain in the temporomandibular joint after the dive. The prevalence of TMD-related symptoms was higher in women before, during, and after the dive. Individuals exhibiting TMD-related symptoms seem to be at the greatest risk of developing pain in the masticatory muscle system and/or the temporomandibular joint during or after the dive.


Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA.
Histone modifications play important roles in regulating DNA-based biological processes. Of the modified sites, histone H3 lysine 56 (H3K56) is unique in that it lies within the globular core domain near the entry-exit sites of the nucleosomal DNA superhelix and its acetylation state in yeast is a marker for newly synthesized histones in transcription, DNA repair, and DNA replication. We now report the presence of H3K56 monomethylation (H3K56me1) in mammalian cells and find that the histone lysine methytransferase G9a/KMT1C is required for H3K56me1 both in vivo and in vitro. We also find that disruption of G9a or H3K56 impairs DNA replication. Furthermore, H3K56me1 associates with the replication processivity factor PCNA primarily in G1 phase of the cell cycle and, directly, in vitro. These results find H3K56me1 in mammals and indicate a role for H3K56me1 as a chromatin docking site for PCNA prior to its function in DNA replication.


Design, synthesis and biological evaluation of novel mansonone E derivatives prepared via CuAAC click chemistry as topoisomerase II inhibitors.
Two series of novel C-9 chloro- and bromo-substituted mansonone E derivatives with triazole moieties at the C-3 position were prepared by using copper-catalysed azide-alkyne cycloaddition click chemistry. These compounds were found as potent inhibitors of topoisomerase II (Topo II) and topoisomerase I (Topo I). The Topo II-mediated pBR322 DNA relaxation and cleavage assay showed that the derivatives might act as catalytic inhibitors. Their cytotoxic activities against A549, HL-60, K562 and HeLa cells were evaluated, indicating that these compounds were potent antitumour agents. Their structure activity relationships and molecular docking study revealed that the substituents of the triazole were particularly important for cytotoxicity.


NLRP7 and related inflammasome activating pattern recognition receptors and their function in host defense and disease.
Host defense requires the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and the induction of pyroptotic cell death, which depends on the activation of inflammatory Caspases within inflammasomes by innate immune cells. Several cytosolic pattern recognition receptors (PRRs) have been implicated in this process in response to infectious and sterile agonists. Here we summarize the current knowledge on inflammasome-organizing PRRs, emphasizing the recently described NLRP7, and their implications in human disease.


Case Report: Spontaneous Rupture of Inferior Epigastric Artery Masquerading as Inguinal Hernia.
Spontaneous rupture of an inferior epigastric artery aneurysm is rare with very few cases reported in the medical literature. Although surgical options are available, this case was managed conservatively with outpatient management. A 29-year-old male presented with right groin pain and swelling that was initially felt to be consistent with an incarcerated inguinal hernia. Further evaluation revealed spontaneous rupture of an inferior epigastric artery aneurysm. The patient was treated conservatively and was ultimately discharged home from the emergency department. Due to the similar clinical presentations, it was important to consider a broad differential to ultimately arrive at the correct diagnosis. In some reported cases of spontaneous epigastric artery aneurysm, surgical intervention was required for control of the bleeding. In our patient, however, conservative management was employed, and the patient was able to be safely discharged with close outpatient follow-up.


Observations on the doubling time of prostate cancer. The use of serial prostate-specific antigen in patients with untreated disease as a measure of increasing cancer volume.
The serum marker prostate-specific antigen (PSA) has been shown to be proportional to the volume of prostate cancer (Yang polyclonal assay). One gram of cancer on average produces 3.5 ng/ml of PSA elevation. Thus, changes in PSA in untreated patients should reflect tumor growth rate and the shape of the growth curve. Forty-three patients with previously untreated prostate cancer had serial PSA determinations during a period of at least 12 months (mean, 30 months; range, 12-63 months). There was no treatment between the initial and final PSA. PSA was measured five or more times in half of these patients. Log-PSA values were plotted versus time, tested for linearity, and compared between different clinical stages and histologic grades. PSA values increased with time in 86% of patients but remained stable in 14%. The increase of PSA was exponential (log-linear) throughout the measured interval. Doubling times were faster in patients with higher disease stages and grades. Seventy-nine percent of all patients had a doubling time of more than 24 months. Twenty of 28 cancers thought to be clinically organ confined doubled at rates exceeding 48 months. Tumor doubling times were overestimated in patients with large-volume benign prostatic hyperplasia because hyperplasia increases serum PSA at an average rate of 0.3 ng/ml. The authors conclude that prostate cancer has a constant (log-linear) growth rate that is very slow. This extraordinarily slow doubling time has substantial consequences for therapeutic decisions and for screening programs.


New oligomers of conduritol-F and muco-inositol. Synthesis and biological evaluation as glycosidase inhibitors.
Several oligomers possessing the configuration of conduritol-F and muco-inositol have been prepared and tested against six glycosidase enzymes. Electrochemical dehalogenation and reductive deprotection of cinnamyl ethers are featured in the reported syntheses. The synthesis, properties, and biological activities are investigated.


Birth Rate Transition in the Republic of Korea: Trends and Prospects.
In Korea, the birth rate is declining at an alarming pace. This study aimed to investigate the changes and trends in the population count, number of births, and birth rate in Korea, in the past and future. Data regarding the total number of births, crude birth rate, and total fertility rate were collected from the "Statistics Korea Census" of the national statistical portal, census report, and Statistics Korea's "2020 Population Trend Survey for 1981-2020, provisional results of birth and death statistics." We used the Organisation for Economic Co-operation and Development 2019 Family Database for the TFR. To develop a better understanding of the data in this study, we classified it according to the modern history of Korea. The changes and trends in the number of births and fertility rate in Korea, after liberation, were due to the birth control policy that restricted births. In Korea's low fertility society, which began in the mid-2000s, the fertility rate dropped to below 0.84 in 2020, despite policies to improve the quality of the population. The death toll has reached 300,000, entering an era of population decline. As we enter the era of population decline, we are in a direction that will cause various socioeconomic problems, from demographic problems to future population decline.


Streptococcal infection and immune response in children with Tourette's syndrome.
Streptococcal infection and basal ganglia inflammation are hypothesized to be involved in Tourette's syndrome (TS). There is a need for effective therapies for managing TS. We studied streptococcal infection and immunity in TS following immunomodulator (pidotimod) therapy. Blood samples from 58 patients with TS and 128 age-matched healthy controls enabled measurement of antistreptolysin O (ASO), T cells, natural killer (NK) cells, interleukin-6 (IL-6) and interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Forty-four patients with abnormal T cell numbers were divided into two groups and treated with pidotimod granules (pidotimod group, n = 20) or pidotimod plus dopaminergic receptor antagonists (combination group, n = 24). Yale Global Tic Severity Scale (YGTSS) scores and immunologic indices were assessed after treatment. An ASO >1:200 was found in 22.4% of children with TS, 7.5% of controls, and 38.9% of children with both TS and attention deficit hyperactivity disorder (ADHD) compared to 15.0% of children with TS alone (P < 0.05). Children with TS showed decreased CD3(+) and CD4(+) T cells, CD4(+)/CD8(+) ratio, IL-6 and IL-8, increased NKC and TNF-α (P < 0.05) as compared to controls. ASO-positive children with TS had lower CD4(+) T cells as compared to ASO-negative children with TS, and lower IL-6 and IL-8 levels as compared to controls (P < 0.05). After 8 weeks of pidotimod treatment, IL-8 was increased compared to either tiapride hydrochloride or haloperidol and pidotimod (P < 0.05). Streptococcal infection in TS patients is associated with immune and cytokine dysfunction, which can be potentially managed with immunomodulator therapy.


Unravelling Alkali-Metal-Assisted Domain Distribution of Quasi-2D Perovskites for Cascade Energy Transfer toward Efficient Blue Light-Emitting Diodes.
Solution processable quasi-2D (Q-2D) perovskite materials are emerging as a promising candidate for blue light source in full-color display applications due to their good color saturation property, high brightness, and spectral tunability. Herein, an efficient energy cascade channel is developed by introducing sodium bromide (NaBr) in phenyl-butylammonium (PBA)-containing mixed-halide Q-2D perovskites for a blue perovskite light-emitting diode (PeLED). The incorporation of alkali metal contributes to the nucleation and growth of Q-2D perovskites into graded distribution of domains with different layer number <n>. The study of excitation dynamics by transient absorption (TA) spectroscopy confirms that NaBr induces more Q-2D perovskite phases with small n number, providing a graded energy cascade pathway to facilitate more efficient energy transfer processes. In addition, the nonradiative recombination within the Q-2D perovskites is significantly suppressed upon Na+ incorporation, as validated by the trap density estimation. Consequently, the optimized blue PeLEDs manifest a peak external quantum efficiency (EQE) of 7.0% emitting at 486 nm with a maximum luminance of 1699 cd m-2 . It is anticipated that these findings will improve the understanding of alkali-metal-assisted optimization of Q-2D perovskites and pave the way toward high-performance blue PeLEDs.


Usefulness of epithelial membrane antigen (EMA) to discriminate between perineural invasion and perineural indentation in prostatic carcinoma.
Perineural invasion (PNI) is one of the few unequivocal criteria to diagnose adenocarcinoma of the prostate. Distinguishing PNI from perineural indentation (PNIn), however, is sometimes difficult. The aim of this study was to discriminate between PNI and PNIn using EMA immunohistochemistry. We selected representative sections from 87 prostatectomies with prostatic adenocarcinoma. Normal peripheral nerves were continuously encircled with perineurium, which was immunoreactive for EMA. We identified 1319 PNI by carcinomas, 368 PNIn by carcinomas, and 303 PNIn by benign glands. We categorized the EMA immunoreactivity patterns into three classes: samples that displayed discontinuity or complete loss of the perineurium (Type A), samples where there were carcinomas or benign glands in the perineural space or peripheral nerves (Type B) and samples that showed no changes in the perineurium (Type C). For PNI we observed Type A, Type B, and Type C patterns in 55.3%, 24.8% and 19.9% of carcinomas, respectively. The incidence of each of those patterns in PNIn by carcinomas was 32.1%, 14.9% and 53.0%, respectively. Cases of PNIn by benign glands showed Type A or Type C patterns. They did not, however, exhibit Type B patterns. EMA immunostaining will aid the diagnosis of prostatic adenocarcinoma.


A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector.
A set of genomic plasmid banks was constructed using the centromere-containing yeast shuttle vector YCp50. The centromere-containing vector is useful for the isolation of genes that are toxic to yeast when present in high copy number. Fourteen independent banks were prepared each with an average representation of two to three times the yeast genome. Any individual plasmid from a given bank is guaranteed to be of independent origin from plasmids obtained from each of the other banks. The banks were constructed from three different size classes of DNA fragments that resulted from varying conditions of partial digestion with Sau3A. This avoided the bias caused by differential sensitivity of sites to cleavage with Sau3A. Insert DNA is sufficiently large that most genes will be present in the set of plasmid banks at a frequency of about 0.1%.


Nanoformulations with exopolysaccharides from cyanobacteria: enhancing the efficacy of bioactive molecules in the Mediterranean fruit fly control.
The increasing demand for food has required intensive use of pesticides which are hazardous to the ecosystem. A valid alternative is represented by biopesticides; however, these molecules are often insoluble in water, and poorly bioavailable. Nanopesticides can be engineered to reach a selected target with controlled release of the active principle. In this work, capsaicin, an irritant alkaloid from hot chili peppers, and hydroxytyrosol, a phenolic compound obtained from extra-virgin olive oil by-products, were loaded into innovative nanocarriers. These were designed ad hoc combining exopolysaccharides from the cyanobacteria Neocyanospira capsulata, and a lipid component, i.e., egg phosphatidylcholine. The polysaccharide was chosen for chemical affinity with the chitin of insect exoskeleton, while the lipids were introduced to modulate the carrier rigidity. The newly formed nanosystems were characterized by physico-chemical techniques and tested for their possible use in pest control programs. The Mediterranean Fruit Fly Ceratitis capitata Wiedemann, 1824 (Diptera, Tephriditae), a pest of the Mediterranean Region causing high economic losses, was used as a model insect. We found that the nanoformulations nanocarriers prepared in this work, were able to increase the ovicidal effect of hydroxytyrosol. Moreover, the formulation encapsulating either hydroxytyrosol or capsaicin were able to reduce the number of females landing on treated apricots.


Minocycline-induced black thyroid with black pigmentation of the thyroid cartilage, cricoid cartilage, and trachea found during reconstructive surgery for hypopharyngeal cancer.
Black thyroid is characterized by a rare pigment change observed almost exclusively in patients taking minocycline. We present the case of a 72-year-old man diagnosed with T3N3bM0 stage IVB hypopharyngeal squamous cell carcinoma who had been taking minocycline for approximately 18 months as a treatment for prurigo chronica multiformis. Initial treatment consisted of total pharyngolaryngoesophagectomy, bilateral neck dissection, total thyroidectomy, pharyngeal reconstruction using a free jejunal autograft, and creation of a permanent tracheostoma. During surgery, black discoloration of the thyroid and trachea was observed. Postoperative histological findings confirmed the black discoloration, with deposits of dark-brown, melanin-like granules observed in the thyroid, trachea, thyroid cartilage, and cricoid cartilage. Therefore, the black discoloration of the thyroid associated with the use of minocycline can extend to the thyroid cartilage, cricoid cartilage, and trachea. This information is important for surgeons to recognize in order to prevent unnecessary resection due to misdiagnosis.


Effect of platelet-rich plasma on meniscus repair surgery: A meta-analysis of randomized controlled trials.
Studies have shown that platelet-rich plasma (PRP) can enhance the effect of meniscus repair, but some studies have suggested different views on the role of PRP. Therefore, a meta-analysis was conducted to determine whether PRP can enhance the effect of meniscus repair with respect to pain reduction and improved functionality and cure rate in patients with meniscus injury. PubMed, EMBASE, Cochrane Library Databases, clinicaltrials.gov, and the CNKI Database were searched from their inception till December 1, 2020. The RCTs reporting the outcomes of the Pain Visual Analog Scale (VAS), Lysholm score, healing rate, and adverse events were included. The risk of bias was assessed using Cochrane collaborative tools. The simulated results were expressed with effect size and 95% confidence interval, and sensitivity and subgroup analysis were performed. The meta-analysis included 8 RCTs and 431 participants. Compared with the control group, use of PRP during meniscus surgery significantly improved the VAS (SMD: -0.40, P = .002, 95%CI: -0.66 to -0.15) and Lysholm score (MD: 3.06, P < .0001, 95%CI: 1.70-4.42) of meniscus injury, but the PRP showed no benefit in improving the healing rate of meniscus repair (RR: 1.22, P = .06, 95%CI: 0.99-1.51). No serious adverse events were reported in any study. PRP is safe and effective in improving the effect of meniscus repair as augment. High quality RCTs with long follow-up and definitive results are needed in the future to confirm the use and efficacy of PRP in meniscus tears.


Prevalence of Carbapenem-Resistant Klebsiella pneumoniae Infection in Southern China: Clinical Characteristics, Antimicrobial Resistance, Virulence, and Geographic Distribution.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains pose a significant threat to public health. In this study, a survey was conducted in the Jiangxi Province of China, covering a total of 140 CRKP strains collected from 11 hospital laboratories from June 2016 to January 2018. All CRKP isolates were subjected to antimicrobial susceptibility testing, capsular serotypes, virulence gene profiles, multilocus sequence typing, and pulsed-field gel electrophoresis. The differences in the patient characteristics and distributions among the various regions were statistically significant (p ≤ 0.001). Most patients were hospitalized in intensive care units (30.0%) and burn departments (13.6%), with lower respiratory (52.1%) and urinary tract (15.7%) infections being most prevalent. A higher ratio of CRKP isolates were identified in the southern and central regions of Jiangxi than in the other regions. Only two carbapenemase genes, blaKPC and blaNDM, were responsible for phenotypic resistance in the tested CRKP strains (46.5% and 22.1%, respectively), among which several major sequence types (STs), such as ST11 (27.8%) and ST23 (14.8%), were identified. A total of 39 virulent strains were detected, of which 22 strains were classified by capsule serotyping. Hypervirulent genes were most common in the eastern and central regions of Jiangxi. In conclusion, CRKP strains in the Jiangxi Province have varied geographic distributions; the resistance rates of isolates harboring blaKPC decreased from southern to northern regions, whereas the drug resistance gene blaNDM showed a tendency to spread from a central point to the surrounding areas. ST23 carbapenem-resistant hypervirulent K. pneumoniae is emerging, resulting in an urgent need to enhance clinical awareness.


Development of the FAST-M maternal sepsis bundle for use in low-resource settings: a modified Delphi process.
To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. Modified Delphi process. Participants from 34 countries. Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. Consensus on bundle items. Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. A maternal sepsis bundle for low resource settings has been developed by international consensus.


Inhibition by L-phenylalanine of tyrosine transport by synaptosomal plasma membrane vesicles: implications in the pathogenesis of phenylketonuria.
The effect of L-phenylalanine on the transport of tyrosine was studied using membrane vesicles from rat brain synaptosomes. Phenylalanine, which is accumulated in phenylketonuria, competitively inhibits tyrosine uptake at concentrations similar to those found in phenylketonuric patients, with a Ki of the same order of the Km for tyrosine. This inhibition could be responsible for the depletion of catecholamines observed in phenylketonuria.


Evidence for separate mechanisms of cytotoxicity in mammalian cells treated with hydrogen peroxide in the absence or presence of L-histidine.
Treating Chinese hamster ovary cells with 1 mM L-histidine markedly increases their susceptibility to killing by H2O2. The mechanism of this effect has not been firmly established, although previous studies have shown that L-histidine in combination with H2O2, in contrast to H2O2 alone, generates DNA double-strand breaks (DSBs), albeit following supralethal concentrations of the oxidant. Using the highly sensitive pulsed field gel electrophoresis technique, we examined the ability of H2O2-L-histidine combinations to induce DSBs in cells over the same oxidant concentration range that causes cytotoxicity. Thus the correlation between DSB induction and cell killing could be investigated directly without the necessity for extrapolating effects across different concentration ranges. We used a number of treatment protocols that allowed the compartmentation of L-histidine inside or outside the cells, or both. Increased cytotoxicity was invariably associated with the appearance of DSBs, and both parameters were dependent on the intracellular fraction of the amino acid. A linear relationship was found between cytotoxicity and DSB formation when the cells were either treated with H2O2 (at > or = 20 microM) and L-histidine concurrently or were exposed to the oxidant following pre-loading with L-histidine. On the other hand, no DSBs were detected in cells treated with: (a) H2O2 alone; (b) L-histidine plus H2O2 at < or = 20 microM; or (c) H2O2 in association with both L-histidine and excess (20 mM) L-glutamine (which prevents L-histidine uptake). Thus, separate mechanisms appear to underlie the cytotoxic response in cells treated with H2O2 in the absence and presence of L-histidine, with the latter process being associated with the induction of DSBs and having a threshold at approximately 20 microM H2O2. The linear correlation between DSBs and cell killing observed in cells treated with H2O2-L-histidine at H2O2 concentrations > or = 20 microM was similar to (but not superimposable on) the correlation curve established for gamma-irradiated cells; DSBs produced by gamma-rays were associated with more cell killing than those generated by the H2O2-L-histidine combination.


[Poster presentations].
Posters have become an essential tool for dissemination of study findings at medical meetings. By presenting a quick snapshot, posters can be an effective means of communicating the main findings of the research quickly and of stimulating rewarding exchanges with the people in attendance. Success depends on catching and holding the attention of passing attendees long enough to establish contact and share knowledge and experience. The purpose of this article is to provide a few guidelines and techniques for preparing and presenting effective and clear research posters at scientific meetings.


Characteristics of Orbital Injuries Associated with Maxillofacial Trauma.
The incidence of ocular injury associated with maxillofacial trauma remains poorly defined, with reported rates ranging from 0.8% to 92%. Our study aims to more accurately characterize ocular injuries associated with midface fractures. We performed a retrospective review of 1677 patients from 2015 to 2020 with midface fractures at a Level I trauma center. Isolated nasal bone and frontal process of the maxilla fractures were excluded. Demographic information, mechanism of injury, need for surgery, and ophthalmologic findings were documented. Statistical analysis was conducted using SPSS. 773 patients between the ages of 15 and 92 were identified. Trauma most commonly resulted from assault (63.8%). The association between the mechanism of injury and ocular injury was statistically significant (p = 0.003), with 78.6% of gunshot wounds and 44.3% of assault patients having an ocular injury. The Ophthalmology service evaluated 62.6% of cases preoperatively. Minor ocular injury occurred in 36% of patients, including 46.1% of isolated orbital floor, and 28.2% of zygomaticomaxillary complex fractures. Major ocular injury occurred in 10.5% of patients. Over 10% of patients with midface fractures were found to have major ocular injuries. Ophthalmologic exams should be performed for all patients with midface fractures to guide clinical decision making and prevent further intraoperative ocular insults. Level 4. This study represents a retrospective cohort study analyzing ocular injuries detected in patients presenting to a Level I trauma center with maxillofacial fractures between 2015 and 2020 Laryngoscope, 133:1624-1629, 2023.


Impairment of trophoblast survival and differentiation by LXR ligands is prevented by cholesterol but not ABCA1 silencing.
The Liver X Receptors (LXRs) drive the transcriptional response to excess intracellular cholesterol. Oxysterols, the products of cholesterol oxidation, are activating ligands for LXR that can accumulate under conditions of oxidative stress and disrupt cholesterol homeostasis. While activation of LXR inhibits trophoblast differentiation, the impact of LXR on trophoblast physiology or cholesterol homeostasis is incompletely understood. We sought to determine if the effects of LXR activation can be ameliorated through modification of cholesterol bioavailability or inhibition of LXR-driven cholesterol efflux in trophoblasts. We measured the effect of oxysterol exposure on BeWo cells and primary human trophoblasts (PHT cells) cultured in lipoprotein-deficient medium. We also measured the effect of the synthetic, LXR-specific ligand T0901317 on PHT cell differentiation and survival. Finally, we silenced the ATP-binding cassette transporter A1 (ABCA1), a transcriptional target of LXR that drives cholesterol efflux, to determine if inhibition of cholesterol efflux could block the effects of T0901317. Oxysterols inhibited BeWo survival and PHT cell differentiation, and these effects were blocked by cholesterol supplementation. T0901317 also inhibited PHT cell differentiation, and this effect was similarly blocked by cholesterol. Unlike cholesterol however, ABCA1 silencing did not modify the effect of T0901317 on PHT cell differentiation. Oxysterols and LXR inhibit trophoblast survival and differentiation exclusively in conditions of cholesterol scarcity. These findings underscore the importance of cholesterol homeostasis in the maintenance of placental function and suggest that pathways regulating cholesterol homeostasis may represent therapeutic targets to mitigate harmful sequelae of placental injury.


Statins and myocardial infarction: Type, dose, and administration time: Does it matter?
Patients with ST-elevation myocardial infarction (STEMI) constitute a vulnerable group that demands the careful assessment and application of all the up-to-date clinical and experimental knowledge, with final aim, the improvement of their prognosis. Statins are an indispensable part of the primary and secondary prevention of coronary artery disease (CAD), not only due to their strong hypolipidemic effect, but also due to their numerous pleiotropic properties that play an important role in the treatment of CAD, especially when the more vulnerable group of STEMI patients is addressed. Nevertheless, there are still issues that require further discussion and clarification, such as the type of statin, the dose of the regimen, the administration time, and the treatment duration.


Anastomosis of the superficial temporal to the middle cerebral artery in the management of an intracranial aneurysm. A case report.
A patient with a subarachnoid haemorrhage due to a large right-sided internal carotid artery aneurysm presented unusual problems in management. Direct obliteration of the aneurysm was not possible, while ligation of the internal carotid artery as an alternative form of treatment necessitated the provision of an alternative collateral blood supply to the right cerebral hemisphere, the anterior circle of Willis being deficient. This case illustrates a new surgical technique which has a place in the management of selected cases of cerebral ischaemic disease.


Trace element geochemistry of the Keana brines field, middle Benue trough, Nigeria.
A trace elements study of various samples from the Keana brines field, middle Benue Trough was carried-out to determine the extent to which Pb-Zn-S and BaSO(4) mineralisations have affected the quality of the brines and the waters in the area. Different sample media such as well-water, pond water, brine spring pool water, stream water, stream sediments etc. were analysed. Geochemical results show that Cu, Zn, Pb, As and S are concentrated in the waters (0.3, 0.36, 0.05, 0.07 and 1 1.5 ppm respectively). These elements are more concentrated in both the spring and pond waters, suggesting that the spring water could have acted as the transport medium for these elements released from deep-seated sources. Transitions elements (Ti, V, Cr, Fe, Co, Ni and Sr) are concentrated in the waters. Compared to the World Health Organization (WHO) admissible limits, the well waters present very high concentrations in Cd (0.56 ppm) and Sb (0.40 ppm) (200x and 70x WHO admissible values respectively). There is a preferential concentration of transition elements (Ti, V, Fe, Co and Ni) in the sediments (41.38, 362, 52.21, 269 and 54 ppm respectively) than in the waters (0.70, 0.05, 5.6, 0.04 and 0.02 ppm respectively). Similarly, Cu, Zn, Pb and As are concentrated in the sediments (44, 72, 41 and 14 ppm respectively). The concentrations of transition elements (Ti, V, Cr, Fe, Co and Ni) in the refined salt were highly elevated (784, 363, 283, 105, 59.2 and 42.6 ppm respectively) (7000-10,000x well water). Similarly, the concentrations of As, Pb, Br and Sr in the refined salt were also alarming (11.6, 16.4, 16.4 and 122 ppm respectively), (1000, 700, 3000 and 20,000x well water values respectively). S on the other hand is absent. One of the striking features is the absence of I, Cd, Sb and Se in the refined salt crystals which were detected in the waters and the brines. Compared to WHO admissible values, the refined salt crystal concentrations for Ni (426 ppm) and Cr (283 ppm) were also very high (2000x WHO values respectively) and to a lesser extent Cu (26.9 ppm) and Zn (21.7 ppm) (12 and 7x WHO values respectively).


Human Papillomavirus (HPV) Vaccination Motivators, Barriers, and Brochure Preferences Among Parents in Multicultural Hawai'i: a Qualitative Study.
The human papillomavirus (HPV) vaccine can prevent cervical and other cancers. Unfortunately, according to the National Immunization Survey-Teen 2014 data, completion of the HPV vaccine was only 38 % for 13- to 17-year-old girls and 31 % for 13- to17-year-old boys in the USA, and prevalence was similar in Hawai'i. Parents' acceptability of the HPV vaccine is critical for the vaccine uptake, and this can be increased by educational materials and interventions. However, HPV materials are not widely distributed in Hawai'i. The purpose of this qualitative study was to identify HPV vaccination barriers, motivators, and brochure preferences among parents of teens in multicultural Hawai'i. Twenty parents were interviewed in person or by telephone. Four major themes emerged: (1) the physician is critical in the decision to vaccinate, (2) parental perception of the child's sexual activity guides the timing of their willingness to vaccinate, (3) HPV health education materials should be provided and discussed by the physician, and (4) parents would prefer an educational brochure that features local faces and testimonials, includes an immunization chart, and addresses barriers to vaccination. These findings informed the development of HPV health education materials tailored to Asian Americans and Pacific Islanders in Hawai'i.


Water, sodium and acid-base balance in premature infants: therapeutical aspects.
One of the main targets of fluid therapy in premature infants is to avoid variations in osmolality, which mainly means providing a stable sodium, glucose, and acid-base balance. Water, sodium, and acid-base balance were measured in 20 infants appropriate-for-gestational age with a gestational age less than or equal to 34 weeks. The infants were randomly assigned to one of two treatment groups. Fluid intake was restricted and air humidity in the incubator was high in order to minimize insensible water loss. Sodium intake in Group 1 was 2 mmol/kg/day and consisted of sodium chloride. Sodium intake in Group 2 was 4 mmol/kg/day and consisted of both sodium chloride and acetate. Weight loss was appropriate in both groups. In the high sodium intake group there was a tendency towards a more stable plasma sodium concentration than in the low sodium intake group. The use of sodium acetate was efficient and practical as normal acid-base balance was maintained. The protocol with restricted fluid intake (1st day 50 ml/kg, 2nd day 70 ml/kg, 3rd day 90 ml/kg, and 4th day 110 ml/kg), high air humidity, a sodium supply of 3 to 4 mmol/kg/day, and a slow correction of metabolic acidosis with sodium acetate, yields suitable guidelines in planning fluid and electrolyte therapy in premature infants less than or equal to 34 weeks' gestation.


Combined immunofluorescence, RNA fluorescent in situ hybridization, and DNA fluorescent in situ hybridization to study chromatin changes, transcriptional activity, nuclear organization, and X-chromosome inactivation.
Epigenetic mechanisms lead to the stable regulation of gene expression without alteration of DNA and trigger initiation and/or maintenance of cell-type-specific transcriptional profiles. Indeed, modulation of chromatin structure and the global 3D organization of the genome and nuclear architecture participate in the precise control of transcription. Thus, dissection of these epigenetic mechanisms is essential for our understanding of gene regulation. In this chapter, we describe challenging combinations of immunofluorescence, and RNA and DNA fluorescent in situ hybridization and their application to our studies of a remarkable example of epigenetic control of gene expression in female mammals, the process of X chromosome inactivation.


Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning.
In this study we have determined the frequency and distribution of interleukin 2 (IL2)-producing cells and their precursors (IL2-P) in the two major subsets of human T cells. The two subsets were identified on the basis of their reactivity (or lack thereof) with anti-T4 or anti-T8 monoclonal antibodies. T4+T8- and T4-T8+ cells were first isolated from peripheral blood T cell populations by positive or negative selection using the fluorescence-activated cell sorter, and then analyzed for total IL2-P and cytolytic T lymphocyte precursor (CTL-P) frequencies using a limiting dilution microculture system which allows clonal growth of every T cell. The results indicated that 50-60% of peripheral blood T cells consisted of IL2-P. In the T4+T8- subset (which represents 60-65% of all T cells) about 75% of the cells were IL2-P, whereas about 15% of T4-T8+ cells exhibited this functional potential. In contrast, about 3% and greater than 95% of T4+T8- and T4-T8+ cells, respectively, were CTL-P. Thus, these data provide direct evidence that there is no absolute correlation between the surface phenotype and the functional potential of human peripheral blood T cells. Moreover, it is evident from this frequency analysis that a significant proportion of T4-T8+ cells have a dual functional potential. IL2-P and CTL-P frequencies were also determined in T cell populations which had been activated in allogeneic mixed lymphocyte culture. The IL2-P frequencies in total T, T4+T8- and T4-T8+ MLC populations were 30, 45 and 10%, respectively. Comparative analysis of IL2 production and CTL activity at the clonal level confirmed that up to 20% of alloreactive CTL with the T4-T8+ surface phenotype were able to produce IL2 upon specific stimulation. This dual functional capacity was also observed among T4+T8- CTL.


The Role of P2Y6 Receptors in the Mechanisms of the Neuroprotective Effect of Citicoline.
Spontaneous bioelectrical activity of the brain and the duration of gasping were recorded in mice during modeling of global strangulation ischemia of the brain against the background of preventive administration of citicoline. The maximum neuroprotective effect of citicoline was observed when it was administered 60 min before the simulation of ischemia and was completely prevented by preliminary administration of a selective P2Y6 receptor antagonist MRS2578. The obtained experimental data attest to the leading role of receptor mechanisms in the implementation of neuroprotective activity of citicoline.


Effect of IL-4, IFN-gamma and IL-12 on cytokine production from human CD45RA and CD45RO CD4 T cell precursors.
The aim of this study was to compare the effects of IL-4, IL-12 and IFN-gamma on the production of T helper-1 (Th1) and T helper-2 (Th2)-type cytokines from human peripheral blood 'naive' CD45RA and 'memory' CD45RO CD4 T cells. CD45RA or CD45RO CD4 T cells were cultured for 4 days with phorbol myristate acetate (PMA) and ionomycin and either IL-4, IFN-gamma or IL-12 and their ability to proliferate and secrete IFN-gamma and IL-4 determined. Purified CD45RO CD4 T cells stimulated with PMA and ionomycin secreted higher levels of IL-4 and IFN-gamma, as measured by ELISA, than CD45RA CD4 T cells which secreted little IL-4 or IFN-gamma. However, CD45RA and CD45RO CD4 T cells proliferated to the same extent and IL-4, IFN-gamma and IL-12 had no effect on this. IL-12 and IFN-gamma had no effect on the amount of IL-4 secreted by PMA and ionomycin-stimulated CD45RO CD4 T cells, but culture with IL-4 enhanced IL-4 production 7-fold. IL-12 increased the amount of IFN-gamma produced by CD45RO CD4 T cells 2- to 3-fold. Small amounts of IFN-gamma production were induced in CD4 CD45RA T cells by IL-12 and IFN-gamma. These results indicate: (1) that CD45RA cells cannot make significant amounts of IL-4 under the conditions used, (2) that CD45RO cells can produce both Th1 and Th2 cytokines immediately upon restimulation, (3) that IL-12 favours Th1 cytokine production in both CD45RA and CD45RO CD4 T cells, and (4) that IFN-gamma favours IFN-gamma production in CD45RA but not CD45RO cells.


Physical activity in gestational trimesters and perinatal outcomes in SUS puerperal women.
Test the association between the practice of physical activity (PA) according to the gestational trimesters and the occurrence of cesarean delivery, prematurity, and low birth weight in puerperal women assisted in the Unified Health System of Santa Catarina, Brazil. A cross-sectional study was conducted with a probabilistic sample of puerperal women who gave birth in public maternity hospitals in Santa Catarina from January to August 2019. The cesarean delivery outcome was self-reported, and information on premature birth (< 37 gestational weeks) and low birth weight (< 2,500 grams) were obtained from medical records. The practice of PA during pregnancy and according to each trimester was self-reported. Multivariate Logistic Regression analyses and interviews with 3,580 puerperal women were carried out. PA practice during any period of pregnancy was reported by 20.6% of the sample, with a gradual reduction in prevalence according to the gestational trimester (16.2%, 15.4%, and 12.8%). The highest prevalences of outcomes concerning the total sample were observed in puerperal women who did not practice PA in the third trimester, with 43.9% for cesarean delivery, 7.7% for low birth weight, and 5.5% for premature birth. The odds of cesarean delivery (OR = 1.40; 95%CI 1.10-1.76) and low birth weight (OR = 1.99; 95%CI 1.04-3.79) were, respectively, 40% and 99% higher among puerperal women who did not practice PA in the third trimester of pregnancy when compared to those who practiced PA. There was no association between PA practice and prematurity. Puerperal women who did not practice PA in the third trimester of pregnancy were more likely to have cesarean delivery and low birth weight newborns.


A theoretical kinetic analysis of the protective action exerted by eserine and other carbamate anticholinesterases against poisoning by organophosphorus compounds.
The protection exerted by carbamate anticholinesterases against the lethal effects of organophosphate anticholinesterases is interpreted kinetically. The protective action is shown to depend on the provision (by carbamylation) of a pool of sequestered cholinesterase resistant to organophosphates but which furnishes (by decarbamylation) sufficient active enzyme to essential cholinergic synapses to ensure survival until all free organophosphate is cleared from the tissues. The two main factors governing the extent of protection are the minimum cholinesterase activity compatible with survival and the "enzyme conservation index" defined essentially as the ratio of the rate of enzyme decarbamylation to the rate of enzyme phosphorylation; the lower the "minimum essential cholinesterase" and the higher the "enzyme conservation index", the greater the protection. The theory is shown to be in excellent qualitative agreement with experiment.


A Belgian consensus on the definition of a treat-to-target outcome set in psoriasis management.
Treat-to-target (T2T) is an algorithm to reach a predefined outcome. Here, we define a T2T outcome for moderate-to-severe psoriasis vulgaris. Briefly, the study included a literature review, discussions with key opinion leaders, recruitment of additional dermatologists with experience in managing moderate-to-severe psoriasis, 3 eDelphi survey rounds and a patient focus group. Relevant topics were selected during discussions prior to the survey for the statements. Surveys were based on the eDelphi methodology for consensus-building using a series of statements. Consensus was defined as at least 80% of participants agreeing. A psoriasis patient focus group provided feedback on topic selection and outcome. A total of 5 discussions were held, and 3 eDelphi rounds were conducted with an average of 19 participants per round. The T2T outcome was set assuming shared decision between patient and dermatologist, awareness and referral for comorbidities by the dermatologist and appropriate treatment adherence by the patient. We defined 'ideal' and 'acceptable' targets; the latter referring to conditions restricting certain drugs. The T2T outcome was multidimensional, including ≥ ΔPASI90/75 or PGA ≤ 1, itch VAS score ≤ 1, absence of disturbing lesions, DLQI ≤ 1/3, incapacity daily functioning VAS score ≤ 1, safety ≤ mild side-effects and full/mild tolerability of treatment for the ideal and acceptable target, respectively. Finally, time to achieve the T2T outcome was set at 12 weeks after initiation for all treatments. At all times, safety should not exceed the presence of mild side-effects. With this novel T2T composite outcome for psoriasis, clinicians and patients can make shared decisions on the treatment goals they envisage, as a guidance for future treatment steps - leading to a tight control management of the disease.