Health risk behaviors and medical sequelae of childhood sexual abuse.
The relationship between childhood sexual abuse and subsequent health risk behaviors and medical problems was examined in 511 women who had used a family practice clinic in a rural midwestern community during a 2-year period (1988 and 1989). These women completed a questionnaire that assessed various health risk behaviors--smoking, drinking, drug abuse, number of sexual partners, and age at first intercourse--and a medical symptom checklist that assessed 38 medical problems related to major systems of body function, the somatization scale from the SCL-90, a screen for sexual abuse, and a brief measure of social support. The results indicated that sexually abused women, who represented 22.1% of the sample, reported significantly more medical problems, greater levels of somatization, and more health risk behaviors than did the nonabused women. More severe abuse (for example, penetration or multiple abusers) correlated with more severe problems. Extent of social support correlated inversely with the number of gynecologic problems reported in the sexually abused group. Fewer than 2% of the sexually abused women had discussed the abuse with a physician. To identify and assist victims of sexual abuse, physicians should become experienced with nonthreatening methods of eliciting such information when the medical history is obtained.


Encapsulation of a CpG oligonucleotide in cationic liposomes enhances its local antitumor activity following pulmonary delivery in a murine model of metastatic lung cancer.
Immunotherapy brings new hope to the fight against lung cancer. General immunostimulatory agents represent an immunotherapy strategy that has demonstrated efficacy with limited toxicity when delivered intratumorally. The goal of this study was to enhance the antitumor efficacy of unmethylated oligodeoxynucleotides containing CpG motifs (CpG) and polyinosinic-polycytidylic acid (poly I:C) double-stranded RNA following their local delivery in lung cancer by encapsulating them in liposomes. Liposomes encapsulation of nucleic acids could increase their uptake by lung phagocytes and thereby the activation of toll-like receptors within endosomes. Liposomes were prepared using a cationic lipid, dioleoyltrimethylammoniumpropane (DOTAP), and dipalmitoylphosphatidylcholine (DPPC), the main phospholipid in lung surfactant. The liposomes permanently entrapped CpG but could not efficiently withhold poly I:C. Both poly I:C and CpG delayed tumor growth in the murine B16F10 model of metastatic lung cancer. However, only CpG increased IFN-γ levels in the lungs. Pulmonary administration of CpG was superior to its intraperitoneal injection to slow the growth of lung metastases and to induce the production of granzyme B, a pro-apoptotic protein, and IFNγ, MIG and RANTES, T helper type 1 cytokines and chemokines, in the lungs. These antitumor activities of CpG were strongly enhanced by CpG encapsulation in DOTAP/DPPC liposomes. Delivery of low CpG doses to the lungs induced increased inflammation markers in the airspaces but the inflammation did not reach the systemic compartment in a significant manner. These data support the use of a delivery carrier to strengthen CpG antitumor activity following its pulmonary delivery in lung cancer.


The area under pH curve: a single-figure parameter representative of esophageal acid exposure.
This investigation aims at providing simpler methods for reading esophageal extended pH-metering tracings. Because the currently used parameters only quantify frequency and duration of acid exposure, we have measured the area between the pH curve and the pH 4 line (area under curve [AUC]) in an attempt to include in the evaluation the severity of acid exposure as well. We compared 20 control and 63 children with gastroesophageal reflux (GER). Extended pH metering curves were read according to currently accepted methods. In addition, we measured planimetrically total 24-hour AUC, AUC during daytime, AUC during sleep time, and total AUC excluding 2-hour postprandial periods. In spite of the very significant differences found between means of controls and GER patients for all variables considered, values overlapped widely. Receiver-operating characteristic (ROC) analysis indicated the best threshold values for differentiation of controls and GER patients and tested the diagnostic efficiency for each variable. We found that 24-hour AUC was the best comprehensive value (sensitivity = 1, specificity = 1) and that there was probably no use for fractional evaluation during selected periods of time. The optimum 24-hour AUC threshold value in the present conditions of measurement (paper speed, 0.25 cm/min; 1 pH unit, 2.5 cm) was 20 cm2. In order to facilitate comparison we propose using a pH-surface unit (pHSU) equal to recording speed (in cm/min) multiplied by vertical shift per 1 pH unit (in centimeters) (in this case, 0.25 x 2.5 = 0.625 cm2). A threshold value of 20 cm2 thus becomes 32 pHSU. A similar transformation will be adequate for any other recording conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of primary aldosteronism in type 2 diabetes mellitus and hypertension: A prospective study from Western India.
Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist; however, underlying primary aldosteronism (PA) can lead to worsening of hypertension, glycemia and cardiovascular risk. We aim to screen patients with T2DM and hypertension for PA by conducting a prospective monocentric study from Western India, which included adults with T2DM and hypertension from the outpatient diabetes clinic. Prospective study. Patients with an aldosterone renin ratio of ≥1.6 ng/dl/µIU/ml with plasma aldosterone concentration (PAC) ≥ 10 ng/dl were considered to be positive on a screening test. A PAC ≥ 6 ng/dl on seated saline suppression test (SST) was used to confirm the diagnosis of PA. Four hundred and eighty-six patients were included in this study. Seventy-six (15.6%, 95% confidence interval [CI]: 12.7%-19.1%) patients had a positive screening test with positive confirmatory test in 20 of the 36 (55.5%, 95% CI: 39.3%-71.7%) screen-positive patients who underwent SST. Patients with positive screening test had a higher proportion of females (65.8% vs. 50%; p = .011), frequent history of hypertensive crises (21.1% vs. 8%; p = .001), uncontrolled blood pressure (51.3% vs. 34.6%; p = .006), diagnosis of hypertension before diabetes (32.9% vs. 21.7%; p = .035) and higher systolic (137.6 ± 6.9 vs. 131.2 ± 17.8 mmHg; p = .004) and diastolic (85.3 ± 11.1 vs. 81.7 ± 10.7 mmHg; p = .007) blood pressures. Patients with positive confirmatory test had longer duration of diabetes (108 [60-162] vs. 42 [24-87] months; p = .012), hypertension (84 [42-153] vs. 36 [15-81] months; p = .038) and higher creatinine (1.16 [1.02-1.42] vs. 0.95 [0.84-1.12] mg/dl; p = .021). PA is prevalent (at least 4.1%) in Asian Indian patients with T2DM and hypertension. Further studies are needed to assess the cost-effectiveness of routine screening.


Prolactinergic neurons in a protochordate.
Peptidergic neurons have been detected in the cerebral ganglion of the ascidian Styela plicata by means of cytochemical methods. After incubation with a mammalian antibody to human prolactin the perikarya show a strong immunoreactivity. The possible function of prolactin-like peptides in the nervous system of protochordates is discussed.


A framework for the continual improvement of health care: building and applying professional and improvement knowledge to test changes in daily work.
We seem to lack a well-defined, comprehensive, and shared understanding of what is required for the continual improvement of health care--at the organizational and the industry levels. This article presents a framework that defines the new body of knowledge which, when joined with the professional knowledge of health care workers, can make continual improvement possible; and gives requirements for building and applying this knowledge to bring about improvement in health care organizations.


Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration.
The requirement and influence of the peripheral nervous system on tissue replacement in mammalian appendages remain largely undefined. To explore this question, we have performed genetic lineage tracing and clonal analysis of individual cells of mouse hind limb tissues devoid of nerve supply during regeneration of the digit tip, normal maintenance, and cutaneous wound healing. We show that cellular turnover, replacement, and cellular differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors. However, regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix. These nerve-dependent phenotypes mimic clinical observations of patients with nerve damage resulting from spinal cord injury and are of significant interest for translational medicine aimed at understanding the effects of nerves on etiologies of human injury.


Delayed subdural hematoma after receiving enoxaparin for prevention of thromboembolic events from high-risk surgery.
Enoxaparin (Lovenox) is a low–molecular weight heparin used to prevent deep venous thrombosis in patients undergoing total hip or knee arthroplasty. Anticoagulation in a patient after trauma may be dangerous and lead to significant hemorrhage. An elderly man fell and sustained a concussion and a hip fracture. His initial computed tomographic scan of the head was normal. He received enoxaparin perioperatively and developed a delayed extensive subdural hematoma. Although enoxaparin has been shown to be an effective and a safe drug for venous thromboembolism prophylaxis in orthopedic surgeries and trauma, severe bleeding may rarely occur, especially in the setting of head trauma. Other therapies for venous thromboembolic prophylaxis, such as mechanical thromboembolism prophylaxis methods, should be considered.


Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.
Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer.


Interpositional elbow arthroplasty using fascia lata autograft in stiff elbow: Case series of 8 patients.
Constrain of a total elbow replacement and elbow arthrodesis are too much for the working population to bear. As such interpositional elbow arthroplasty using fascia lata autologous graft to reconstruct the elbow joint is a viable option in this age group. 8 patients were operated for arthritic stiff elbow, and joint reconstruction was done using fascia lata autologous graft, with out the use of any hinged external fixator. Pre-operative and post-operative functional assessment was done using Mayo Elbow Performance Score (MEPS) and statistically measured using a paired t-test. Result There was significant improvement in range of motion in coronal (flexion-extension) and axial (supination-protonation) with p-value of <0.001. The mean pre-operative MEPI increased from 40.6 points to 91.9 points (p < 0.0001). All parameters of MEPI had statistically significant improvement with exception of stability (p-value = 0.0824).


An epidermal proliferative unit-like structure in the epithelium of mouse bladder observed by backscattered electron imaging.
The simultaneous use of a silver-staining technique, backscattered electron imaging and stereo-tilts has made it possible to visualize the spatial distribution of cell nuclei in the stretched epithelium of the bladder of mice. This study has led to the observation that a structural organization resembling the epidermal proliferative unit, previously found in the skin exists also in bladder epithelium. However, the proliferative unit in the bladder was different in that it contained a higher number of cells per unit, and an absence of columns of inactive squamous cells. These findings may indicate that epidermal proliferative unit-like structures represent a common form of organization in some epithelia.


Effect of portal venous flow augmentation on liver enhancement with CT.
The purpose of this study was to evaluate the effect of portal flow augmentation on hepatic computed tomographic (CT) enhancement. Thirteen patients undergoing follow-up CT of the liver within 6 months of initial study ingested 470 mL of Ensure 30 min before the second examination. Contrast medium injection and scanning parameters were identical for both studies. The time to peak and the maximum and mean liver enhancements were 68 s, 56 HU, and 46 HU, respectively, for the examinations without Ensure and 68 s, 53 HU, and 44 HU for the examinations with Ensure. No significant difference was found between the two groups when mean liver enhancement was calculated over 3-s time intervals. Portal venous flow augmentation induced by a meal had no effect on liver enhancement.


Nature's strategy for optimizing power generation in insect flight muscle.
Table 1 summarizes the primary mechanisms most likely responsible for modifying wing beat frequency (WBF) and muscle power in the Drosophila mutants discussed above. The different outcomes reflect different mechanisms that come into play, depending on the protein and site of the mutation. For example, the reduced muscle power and WBF of the RLC phosphorylation site mutant Mlc2(S6sA,S67A) reflect the reduced number of myosin heads available to form working cross-bridges and the concomitant reduction in muscle stiffness. The mixed results of the other mutants are more difficult to explain. For example, while the reduced muscle stiffness of the paramyosin rod mutant pm(S18A) and the projectin mutant bent(D)/+ may in part reflect mutation-related increases in compliance of the thick filaments (pm(S18A)) or connecting filaments (bent(D)/+), the elevated WBF is unexpected because one would expect reduced muscle stiffness to lower WBF rather than raise it. Other aspects of the results are equally baffling. In the case of pm(S18A), e.g., myofilament kinetics are enhanced, opposite to what one would predict from reduced myofilament stiffness (Wang et al. 1999), but consistent with a direct effect of the mutation on cross-bridge kinetics. It is tempting to speculate that the fly increases the resonance frequency of its flight system, perhaps even over-compensating, as a mechanism for bringing the optimum frequency of power output of the flight system in line with the optimum frequency of power output of the myofilaments in order to achieve flight. The fly might accomplish this by voluntarily activating flight control muscles that change the stiffness and shape of the thoracic box (Tu and Dickinson, 1996), thereby significantly changing the basal stiffness of the resonance system. This effective strategy would serve to tune flight system kinetics to that of the actomyosin motor for optimum power transmission. Notably, of the four thick filament mutations listed in Table 1 produce no significant changes in wing beat frequency, three exhibit reduced muscle power, so these flies must make other adjustments to maintain flight competency. These may be additional cases in which the effects of marked changes in cross-bridge kinetics (MHC IFI-EC), cross-bridge deployment (Mlc2(delta2-46), or sarcomere (thick filament) stiffness (pm(S-A4) and Df(3L) fln(1)/+) are ameliorated by the intervention of direct flight muscles. In summary, it may well be that the fly's general response to mutations that alter one component of the flight system is to alter another in order to maintain optimum transmission of power and flight competency. That is, nature's strategy for optimizing power generation throughout the flight system is probably the same as that at the level of the myofibril: that is, strengthen weak links, orient parts for optimum power production, and modify power train proteins through isoform switches or post-translational modifications to assure all components are in tune with one another.


Biodegradation of insensitive munition (IM) formulations: IMX-101 and IMX-104 using aerobic granule technology.
A laboratory-scale aerobic granular sludge (AGS) sequencing batch bioreactor (SBR) was initiated in this study for the biodegradation of hazardous insensitive munition (IM) formulation constituents; 2,4-dinitroanisole (DNAN), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 1-nitroguanidine (NQ), and 3-nitro-1,2,4-triazol-5-one (NTO). Efficient (bio)transformation of the influent DNAN and NTO was achieved throughout reactor operation with removal efficiencies greater than 95%. An average removal efficiency of 38.4 ± 17.5% was recorded for RDX. NQ was only slightly removed (3.96 ± 4.15%) until alkalinity was provided in the influent media, which subsequently increased the NQ removal efficiency up to an average of 65.8 ± 24.4%. Batch experiments demonstrated a competitive advantage for aerobic granular biofilms over flocculated biomass for the (bio)transformation DNAN, RDX, NTO, and NQ, as aerobic granules were capable of reductively (bio)transforming each IM compound under bulk aerobic conditions while flocculated biomass could not, thus demonstrating the contribution of inner oxygen-free zones within aerobic granules. A variety of catalytic enzymes were identified in the extracellular polymeric matrix of the AGS biomass. 16 S rDNA amplicon sequencing found Proteobacteria (27.2-81.2%) to be the most abundant phyla, with many genera associated with nutrient removal as well as genera previously described in relation to the biodegradation of explosives or related compounds.


Membrane alterations in G6PD- and PK-deficient erythrocytes exposed to oxidizing agents.
After in vitro treatment of normal, glucose-6-phosphate dehydrogenase-deficient or pyruvate kinase-deficient human erythrocytes with three different oxidizing agents, the extent of lipid peroxidative degradation and the alterations of membrane proteins were evaluated. Exposure to tert-butylhydroperoxide induced, most markedly in G6PD- and PK-deficient erythrocytes, a reduction of protein bands 1, 2, 2.1, 3, 4.1, 4.2, and 5, with the appearance of high-molecular-weight aggregates and of "new" polypeptide components in the 29- to 23-kDa region and with a marked increase of membrane-bound globin. Malonyldialdehyde production was highest in G6PD-deficient cells and relatively low in PK-deficient ones. Methylene blue, which had similar but less relevant effects on lipid peroxidation, in G6PD-deficient erythrocytes caused a conspicuous appearance of high-molecular-weight aggregates and a simultaneous relevant decrease of bands 1 and 2 and of membrane-bound globin; it brought about an almost opposite effect in PK-deficient red cells. Acetylphenylhydrazine, which under our conditions appeared the mildest agent, failed, in normal and PK-deficient erythrocytes, to increase malonyldialdehyde production or to alter membrane proteins, whereas it caused, in G6PD-deficient cells, a slight decrease of bands 1 and 2, a more pronounced decrease of band 3, and a marked increase of bands 4.5 and 4.9.


Conjoint glutamic acid decarboxylase 65 and P/Q voltage gated calcium channel antibodies in autoimmune epilepsy: A case report.
Numerous autoantibodies are implicated in the pathogenesis of autoimmune epilepsy. In the past decade, many case series reported the association of glutamic acid decarboxylase 65 (GAD 65) antibodies with epilepsy. Conjoint presence of GAD 65 antibodies with antinuclear, anti-thyroid, and anti-parietal cell antibodies has often been demonstrated. However, concomitant elevated levels of GAD 65 and P/Q voltage gated calcium channel (VGCC) antibodies is rare. We report a case of autoimmune epilepsy with conjoint GAD 65 and P/Q VGCC antibodies in the absence of malignancy. This report highlights a possible role of P/Q VGCC antibodies in the pathogenesis of autoimmune epilepsy.


Trends in General Surgery Resident Experience with Colorectal Surgery: An Analysis of the Accreditation Council for Graduate Medical Education Case Logs.
Colorectal surgery is a core component of general surgery. The volume of colorectal surgery performed by general surgery residents throughout training has not been studied. This study aims to analyze trends observed in colorectal-specific case numbers logged by general surgery residents over 16 years. Case number data for general surgery residents was extracted from the publicly available, annually published Accreditation Council for Graduate Medical Education (ACGME) database from 2003 to 2019. Cases were categorized as open or laparoscopic colectomy/proctectomy, colectomy with ileoanal pull-thru, abdomino-perineal resection (APR), transanal rectal tumor excision (TRE), anorectal procedure, colonoscopy, and total colorectal cases. The average case numbers per category was calculated for each year. Linear regression analyzed trends in case categories for all residents and those logged as surgeon chief and junior residents. ACGME accredited general surgery residency programs. Not applicable. General surgery residents reported increased numbers of all, chief, and junior resident colorectal cases over the study period (124.5-173.7 cases/yr; 38.4-53.0 cases/yr; 86.4-120.6 cases/yr, all p = 0.00). Average cases for all, chief, and junior residents have increased for laparoscopic colectomy/proctectomy (4.6-26.4 cases/year; 2.7-12.9 cases/year; 2.0-13.5 cases/year, all p = 0.00), anorectal surgeries (26.7-37.7 cases/year; 5.4-9.9 cases/year; 21.3-27.8 cases/year, all p = 0.00), and colonoscopies (35.9-70.6 cases/year, p = 0.00; 6.6-14.1 cases/year, p = 0.01; 29.4-56.5 cases/year, p = 0.00). Average cases for all, chief, and junior residents have decreased for open colectomy/proctectomy (52.0-34.9 cases/year; 21.2-14.3 cases/year; 30.9-20.6 cases/year, all p = 0.00), APR (3.3-2.7 cases/year, p = 0.00; 1.8-1.3 cases/year, p = 0.00; 1.5-1.4 cases/year, p = 0.02), TRE (1.9-1.1 cases/year; 0.7-0.4 cases/year; 1.2-0.6 cases/year, all p = 0.00). Ileoanal pull-thru did not demonstrate a linear trend. The increase in exposure to colectomies/proctectomies, anorectal procedures and colonoscopies is encouraging, as these common colorectal operations will be encountered in general surgery practice. The observed low case numbers for TRE, APR, and ileoanal pull-thru suggest a need for specialized training.


Psychometric Properties of the Chinese Version of the Bipolar Depression Rating Scale for Bipolar Disorder.
Unlike unipolar depression, depressive episode of bipolar disorder is often associated with clinical characteristics, such as atypical and mixed symptoms. However, there are currently no valid and reliable specific tools available to assess the specific psychiatric symptomatology of depressive episode of bipolar disorder in China. Therefore, we aimed to evaluate the psychometric properties of the Chinese version of the Bipolar Depression Rating Scale (BDRS) in Chinese patients with bipolar disorder. The sample of this study included 111 patients with bipolar disorder (30 male, 81 female). All participants were interviewed with the Chinese version of the BDRS (BDRS-C), the 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). A psychometric analysis of the BDRS was conducted. The Cronbach's alpha coefficient of the BDRS-C reached a value of 0.869. The BDRS-C score and scores for the HAMD-17 (r = 0.819, p < 0.01), the MADRS (r = 0.882, p < 0.01) and the YMRS (r = 0.355, p < 0.01) exhibited significant positive correlations. Close correlations were observed between the mixed subscale score of the BDRS-C and the YMRS score (r = 0.784, p < 0.01). Exploratory factor analysis resulted in three factors: a primary depressive symptoms cluster, a secondary depressive symptoms cluster, and a mixed symptoms cluster. The Chinese version of the BDRS has satisfactory psychometric properties. This is a valid and reliable instrument to assess depressive symptomatology in patients with bipolar disorder.


Ephrin-B2 reverse signaling is required for topography but not pattern formation of lateral superior olivary inputs to the inferior colliculus.
Graded and modular expressions of Eph-ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin-B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin-B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild-type and ephrin-B2(lacZ/+) mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin-B2(lacZ/+) mutants. By the onset of hearing, both wild-type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin-B2(lacZ/+) mice lack a reliable topography in LSO-IC projections, suggesting that fully functional ephrin-B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin-B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience.


Effects of polypropylene nanofibers on soft corals.
Current information regarding the effects of both micro- and nano-plastic debris on coral reefs is limited; especially the toxicity onto corals from nano-plastics originating from secondary sources such as fibers from synthetic fabrics. Within this study, we exposed the alcyonacean coral Pinnigorgia flava to different concentrations of polypropylene secondary nanofibers (0.001, 0.1, 1.0 and 10 mg/L) and then assayed mortality, mucus production, polyps retraction, coral tissue bleaching, and swelling. The assay materials were obtained by artificially weathering non-woven fabrics retrieved from commercially available personal protective equipment. Specifically, polypropylene (PP) nanofibers displaying a hydrodynamic size of 114.7 ± 8.1 nm and a polydispersity index (PDI) of 0.431 were obtained after 180 h exposition in a UV light aging chamber (340 nm at 0.76 Wˑm-2ˑnm-1). After 72 h of PP exposure no mortality was observed but there were evident stress responses from the corals tested. Specifically, the application of nanofibers at different concentrations caused significant differences in mucus production, polyps retraction and coral tissue swelling (ANOVA, p < 0.001, p = 0.015 and p = 0.015, respectively). NOEC (No Observed Effect Concentration) and LOEC (Lowest Observed Effect concentration) at 72 h resulted 0.1 mg/L and 1 mg/L, respectively. Overall, the study indicates that PP secondary nanofibers can cause adverse effects on corals and could potentially act as a stress factor in coral reefs. The generality of the method of producing and assaying the toxicity of secondary nanofibers from synthetic textiles is also discussed.


Intercostal nerve block with thoracoabdominal incision.
A double-blind study was done on 30 patients undergoing thoracoabdominal incisions for retroperitoneal lymphadenectomy in testicular carcinoma to determine the effect of intraoperative intercostal nerve block with bupivacaine. The postoperative pain, day of ambulation and day of oral fluid intake were analyzed. In this homogeneous group we found a significant reduction in the amount of postoperative analgesia required but no difference in the day of ambulation or fluid intake.


Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study.
Research has shown that chloroquine (CQ) can effectively help control COVID-19 infection. B24N24 nanocage is a drug delivery system. Thus, through density functional theory, the present study analyzed pristine nanocage-CQ interaction and CQ interaction with Si- and Al -doped nanocage. The findings revealed that nanocage doping, particularly with Si and Al, yields more satisfactory drug delivery for CQ due to their greater electronic and energetic characteristics with CQ.


Enhancing phytoremediation of hazardous metal(loid)s using genome engineering CRISPR-Cas9 technology.
Rapid and drastic changes in the global climate today have given a strong impetus to developing newer climate-resilient phytoremediation approaches. These methods are of great public and scientific importance given the urgency of this environmental crisis. Climate change has adverse effects on the growth, outputs, phenology, and overall productivity of plants. Contamination of soil with metal(loid)s is a major worldwide problem. Some metal(loids) are carcinogenic pollutants that have a long half-life and are non-degradable in the environment. There are many instances of the potential link between chronic heavy metal exposure and human disease. The adaptation of plants in the changing environment is, however, a major concern in phytoremediation practice. The creation of climate-resistant metal hyperaccumulation plants using molecular techniques could provide new opportunities to mitigate these problems. Consequently, advancements in molecular science would accelerate our knowledge of adaptive plant remediation/resistance and plant production in the context of global warming. Genome modification using artificial nucleases has the potential to enhance phytoremediation by modifying genomes for a sustainable future. This review focuses on biotechnology to boost climate change tolerant metallicolous plants and the future prospects of such technology, particularly the CRISPR-Cas9 genome editing system, for enhancing phytoremediation of hazardous pollutants.


The mobility of the superficial and deep midfacial fat compartments: An ultrasound-based investigation.
Understanding the mobility of the midface and the separate contributions of the superficial and deep fat compartments is essential for natural esthetic outcomes following soft tissue filler or fat grafting procedures. A study was designed that used ultrasound imaging to demonstrate in vivo visualization and quantification of distances and movements in the midface. A total of 48 midfaces of 24 healthy Caucasian volunteers, all naïve of esthetic procedures, (22 females; 46.85 (9.8) years; 22.83 (3.1) kg/m2 ) were scanned using 18 MHz ultrasound imaging. Distances between bony landmarks (inferior orbital rim, infraorbital foramen) were used as markers to measure the cranial movement of the superficial (superficial nasolabial and superficial medial cheek fat compartment) and the deep (deep pyriform space, deep medial check fat compartment, deep lateral cheek fat compartment) midfacial fat compartments between resting and smiling facial position. The superficial midfacial fat compartment moved, on average, 3.7 mm (p < 0.001) cranially, whereas the deep midfacial fat compartments moved, on average, 0.1 mm (p > 0.05) during smiling. No gender differences in mobility were identified (p > 0.05). The results obtained are in line with previous cadaveric investigations and revealed, in a highly statistically significant fashion, that the superficial midfacial fat compartments move in cranial direction whereas the deep fat compartment did not display similar positional changes. These results help to guide facial injectable treatments and to understand why, in the midface, a deep supraperiosteal approach should be favored when augmenting the deep midfacial fat compartments.


Serial investigation of perfusion disturbances and vasogenic oedema in hypertensive encephalopathy by diffusion and perfusion weighted imaging.
Serial MRI including diffusion and perfusion imaging was performed in a patient with hypertensive encephalopathy. At admission, the patient was disorientated and presented with seizures and cortical blindness. Perfusion imaging showed a marked reduction in blood volume and flow, with corresponding vasogenic oedema in the occipital, posterior temporal, and, to a lesser extent, frontal lobes. The clinical symptoms disappeared rapidly following treatment, whereas the disturbed circulation pattern and vasogenic oedema resolved more slowly. A complete normalisation was seen after 1 year.


Modulation of paracetamol and nefopam antinociception by serotonin 5-HT(3) receptor antagonists in mice.
Post-operative nausea and vomiting are common adverse events that require administration of anti-emetic compounds, such as the serotonin 5-HT(3) receptor antagonists, but these drugs can also reduce the analgesic efficacy of some analgesics (paracetamol, tramadol). The present study was designed to explore the effect of 3 serotonin 5-HT(3) receptor antagonists on the antinociceptive efficacy of another frequently used post-operative analgesic, nefopam, in the mouse writhing and formalin tests. Pre-treatment with tropisetron, ondansetron or MDL72222 did not significantly modify nefopam antinociception in both tests. However, paracetamol antinociception was blocked by ondansetron in the formalin test. These results provide a rationale for the clinical use of nefopam with anti-emetics during surgery.


Prediction of patient's neurological recovery from cervical spinal cord injury through XGBoost learning approach.
Due to the diversity of patient characteristics, therapeutic approaches, and radiological findings, it can be challenging to predict outcomes based on neurological consequences accurately within cervical spinal cord injury (SCI) entities and based on machine learning (ML) technique. Accurate neurological outcomes prediction in the patients suffering with cervical spinal cord injury is challenging due to heterogeneity existing in patient characteristics and treatment strategies. Machine learning algorithms are proven technology for achieving greater prediction outcomes. Thus, the research employed machine learning model through extreme gradient boosting (XGBoost) for attaining superior accuracy and reliability followed with other MI algorithms for predicting the neurological outcomes. Besides, it generated a model of a data-driven approach with extreme gradient boosting to enhance fault detection techniques (XGBoost) efficiency rate. To forecast improvements within functionalities of neurological systems, the status has been monitored through motor position (ASIA [American Spinal Injury Association] Impairment Scale [AIS] D and E) followed by the method of prediction employing XGBoost, combined with decision tree for regression logistics. Thus, with the proposed XGBoost approach, the enhanced accuracy in reaching the outcome is 81.1%, and from other models such as decision tree (80%) and logistic regression (82%), in predicting outcomes of neurological improvements within cervical SCI patients. Considering the AUC, the XGBoost and decision tree valued with 0.867 and 0.787, whereas logistic regression showed 0.877. Therefore, the application of XGBoost for accurate prediction and decision-making in the categorization of pre-treatment in patients with cervical SCI has reached better development with this study.


Mechanochemical synthesis of an elusive fluorinated polyacetylene.
Polymer mechanochemistry has traditionally been employed to study the effects of mechanical force on chemical bonds within a polymer backbone or to generate force-responsive materials. It is under-exploited for the scalable synthesis of wholly new materials by chemically transforming the polymers, especially products inaccessible by other means. Here we utilize polymer mechanochemistry to synthesize a fluorinated polyacetylene, a long-sought-after air-stable polyacetylene that has eluded synthesis by conventional means. We construct the monomer in four chemical steps on gram scale, which involves a rapid incorporation of fluorine atoms in an exotic photochemical cascade whose mechanism and exquisite stereoselectivity were informed by computation. After polymerization, force activation by ultrasonication produces a gold-coloured, semiconducting fluoropolymer. This work demonstrates that polymer mechanochemistry is a valuable synthetic tool for accessing materials on a preparative scale.


Enantioselective allylation of α,β-unsaturated aldehydes with allyltrichlorosilane catalyzed by METHOX.
α,β-Unsaturated aldehydes 6a-j undergo an enantioselective allylation with allylic trichlorosilanes 2a,b in the presence of METHOX (4) as a Lewis basic catalyst (≤10 mol %) to produce the homoallylic alcohols 7a-l at good to high enantioselectivity (83-96% ee). This study shows that the reactivity scope of METHOX can be extended from aromatic to nonaromatic aldehydes.


Cause of intrauterine and neonatal death in twin pregnancies (CoDiT): development of a novel classification system.
Twin pregnancies have a significantly higher perinatal mortality than singleton pregnancies. Current classification systems for perinatal death lack twin-specific categories, potentially leading to loss of important information regarding cause of death. We introduce and test a classification system designed to assign a cause of death in twin pregnancies (CoDiT). Retrospective cross-sectional study. Tertiary maternity unit in England with a perinatal pathology service. Twin pregnancies in the West Midlands affected by fetal or neonatal demise of one or both twins between 1 January 2005 and 31 December 2016 in which postmortem examination was undertaken. A multidisciplinary panel designed CoDiT by adapting the most appropriate elements of singleton classification systems. The system was tested by assigning cause of death in 265 fetal and neonatal deaths from 144 twin pregnancies. Cause of death was validated by another obstetrician blinded to the original classification. Inter-rater, intra-rater, inter-disciplinary agreement and cause of death. Cohen's Kappa demonstrated 'strong' (>0.8) inter-rater, intra-rater and inter-disciplinary agreement (95% CI 0.70-0.91). The commonest cause of death irrespective of chorionicity was the placenta; twin-to-twin transfusion syndrome (TTTS) was the commonest placental cause in monochorionic twins and acute chorioamnionitis in dichorionic twins. This novel classification system records causes of death in twin pregnancies from postmortem reports with high inter-user agreement. We highlight differences in aetiology of death between monochorionic and dichorionic twins. New classification system for #twin cause of death 'CoDiT' shows high rater agreement.


Pollutants removals and energy consumption in electrochemical cell for pulping processes wastewater treatment: Artificial neural network, response surface methodology and kinetic studies.
Response surface methodology (RSM) and artificial neural network (ANN) were used for modelling the electrocoagulation removal of pollutants from wastewater from pulping processes. The Design of Experiment based on central composite design was used to investigate the combine effects of pH (5.4-9.0), time (10-45 min) and current density (j) (9-39 mA/m2), on the removal efficiency of the Chemical Oxygen Demand (COD), Total Dissolve Solids (TDS) as well as Turbidity while Energy consumption (EC) was estimated per kg [COD] removed. The kinetics of the process was modelled with pseudo first and second order models. The removability of the COD, TDS and Turbidity were found to be 76.4, 57.0 and 97.13% with Energy consumption of 2.72 kWh/kg[COD] at optimal pH 6.83, current density of 22.06 mA/m2, and reaction time of 45 min. The ANN model gave a better fitting of the electrocoagulation process than the RSM, considering the R2 of 0.999 and MSE of 0.00753 obtained for the former. The pseudo first order model gave a better analysis of the kinetic data. The characterization of the sludge produced showed the potential of its use as adsorbent for organic or mineral contaminants and recovery of aluminium and other metals. Thus, electrocoagulation with monopolar aluminium electrodes displayed effective and a viable alternative for the pollutants removal from pulp processing wastewater.


[Hydromorphone--review of pharmacological properties and therapeutic efficacy with special regard to a controlled release preparation].
Hydromorphone is a micro receptor agonist opioid. According to WHO recommendations, hydromorphone is to be classified in step III of pain therapy. An oral formulation with a prolonged duration of action of 12 hours has been evaluated only recently. The controlled release capsule is especially suited for the regular twice a day administration in cases of severe and persistent pain. The oral formulation of hydromorphone increases the number of opioid analgesics available for pain therapy in step III. Hydromorphone is recommended when morphine fails to produce sufficient pain relief (despite increase of doses) or causes intolerable side effects (despite treatment of symptoms). In principle, no differences in efficacy of morphine and hydromorphone are to be expected. However, clinical experience shows that changing one opioid analgesic to another one can improve the treatment of patients so that hydromorphone may replace another opioid analgesic to which a patient fails to respond well or develops side effects. The dose of hydromorphone equivalent to 2 times 30 mg controlled release morphine is about 2 times 4 mg. The values for the absorption, bioavailability and maximum plasma concentration after the administration of controlled release hydromorphone every 12 hours -of three times the dose- are equivalent to those of an immediate release tablet given every 4 hours. In several open label and controlled studies, hydromorphone proved to be of good efficacy in the treatment of acute and persistent pain, especially in patients with severe cancer pain. With regard to the incidence of side effects, no significant differences between morphine and hydromorphone could be established. In general, the side effects of hydromorphone are typical for opioid analgesics. In conclusion, controlled release hydromorphone seems to be well suited for the control of severe chronic pain when given twice daily.


Validation study of the ACS NSQIP surgical risk calculator for two procedures in Japan.
The ACS NSQIP Surgical Risk Calculator (SRC) assesses risk to support goal-concordant care. While it accurately predicts US outcomes, its performance internationally is unknown. This study evaluates SRC accuracy in predicting mortality following low anterior resection (LAR) and pancreaticoduodenectomy (PD) in NSQIP patients and accuracy retention when applied to native Japanese patients (National Clinical Database, NCD). NSQIP (41,260 LAR; 15,114 PD) and NCD cases (61,220 LAR; 27,901 PD) from 2015 to 2017 were processed through the SRC mortality model. Country-specific calibration and discrimination were assessed with and without an intercept correction applied to the Japanese data. The SRC exhibited acceptable calibration for LAR and PD when applied to NSQIP data but miscalibration for NCD data. A simple correction to the model intercept, motivated by lower mortality rates in the Japanese data, successfully remediated the miscalibration. The SRC may inaccurately predict surgical risk when applied to the native Japanese population. An intercept correction method is suggested when miscalibration is encountered; it is simple to implement and may permit effective international use of the SRC.


The p90 ribosomal S6 kinase-UBR5 pathway controls Toll-like receptor signaling via miRNA-induced translational inhibition of tumor necrosis factor receptor-associated factor 3.
MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. For example, miRNAs repress gene expression by recruiting the miRNA-induced silencing complex (miRISC), a ribonucleoprotein complex that contains miRNA-engaged Argonaute (Ago) and the scaffold protein GW182. Recently, ubiquitin-protein ligase E3 component N-recognin 5 (UBR5) has been identified as a component of miRISC. UBR5 directly interacts with GW182 proteins and participates in miRNA silencing by recruiting downstream effectors, such as the translation regulator DEAD-box helicase 6 (DDX6) and transducer of ERBB2,1/2,2 (Tob1/2), to the Ago-GW182 complex. However, the regulation of miRISC-associated UBR5 remains largely elusive. In the present study, we showed that UBR5 down-regulates the levels of TNF receptor-associated factor 3 (TRAF3), a key component of Toll-like receptor signaling, via the miRNA pathway. We further demonstrated that p90 ribosomal S6 kinase (p90RSK) is an upstream regulator of UBR5. p90RSK phosphorylates UBR5 at Thr637, Ser1227, and Ser2483, and this phosphorylation is required for the translational repression of TRAF3 mRNA. Phosphorylated UBR5 co-localized with GW182 and Ago2 in cytoplasmic speckles, which implies that miRISC is affected by phospho-UBR5. Collectively, these results indicated that the p90RSK-UBR5 pathway stimulates miRNA-mediated translational repression of TRAF3. Our work has added another layer to the regulation of miRISC.


Orientation mechanisms and sensory organs involved in host location in a dipteran parasitoid larva.
The robber fly Mallophora ruficauda is one of the principal pests of apiculture in the Pampas region of Argentina. Larvae are solitary ectoparasitoids of third-instar scarab beetle larvae. Females of M. ruficauda do not lay eggs on or near the hosts, but on tall grasses. After hatching, larvae are dispersed by the wind and drop to the ground, where they dig and search for potential hosts. It is known that second-instar larvae of M. ruficauda exhibit active host-searching behaviour towards their preferred hosts, i.e., third-instar larvae of Cyclocephala signaticollis. Although host-location seems to be mediated by chemical cues, the mechanism of orientation and the sensory organs involved in host location remain unknown. We carried out behavioural experiments in the laboratory to address these questions. We also tested whether the orientation behaviour is exclusively based on the use of chemical cues. We found that larvae of M. ruficauda detect the chemicals with chemosensilla on the maxillary palps. Only one maxillary palp suffices for orientation, but their bilateral ablation abolishes orientation. Besides, an hexane extract of the host body was as attractive as a live host. Our results support that M. ruficauda larvae find their hosts underground by means of chemoklinotaxis.


Wound sterilization: CO2 laser versus iodine.
Control of infection in a surgical wound remains a challenge, especially if further surgery in the area is needed. This study was designed to compare the effectiveness of sterilization of a standard experimental infected wound by surgical skin preparation (Betadine) as compared to treatment with the CO2 laser. Standard wounds (5 x 6 cm) were created superficial to the panniculus carnosus on each flank of 37 adult male New Zealand rabbits. Each wound was infected with a standard dose of Pseudomonas aeruginosa. All wounds became grossly infected. On the third day one flank wound was treated with the CO2 laser, the other with the Betadine solution, and a punch biopsy (4 mm) was taken from each wound for quantitative bacterial counts. Less than 10% of the laser-treated wounds grew Pseudomonas, whereas nearly 40% of the iodine-treated wounds remained infected (P less than 0.005). Our early clinical experience using the CO2 laser for the sterilization of infected wounds is also reported.


Triamcinolone acetonide-chitosan coated liposomes efficiently treated retinal edema as eye drops.
Macular edema (ME), which is present in various retinal diseases, leads to permanent retinal structural damage and threatens vision. The intravitreal/periocular injection of triamcinolone acetonide (TA) can improve the prognosis of ME; however, further exploration of noninvasive delivery systems is essential. Therefore, as a continuation of our previous study using TA-chitosan coated liposomes (TA-CHLs) as a topical drug delivery system, the present study aimed to determine the drug safety, stability, permeability, and bioavailability of TA-CHLs. The study was based on detecting the delivery of a fluorescent dye to the retina using optical coherence tomography angiography in rats. Marked cellular uptake was observed in cell lines. TA-CHL toxicity was investigated in cell culture. Clinical ocular safety was evaluated by measuring the corneal thickness and intraocular pressure. In preclinical studies on a laser-induced retinal edema rat model, the TA-CHL eye drops had dramatic therapeutic effect in remission of retinal edema over 10 days. These results demonstrated that TA-CHL was nontoxic and had good bioavailability in vitro and in vivo. The results of the present study indicated that this formulation could be an effective therapeutic approach and the TA-CHL eye drops may represent a new option for retinal diseases.


Comparison of patient-controlled analgesia with and without a background infusion after appendicectomy in children.
There have been many studies using patient-controlled analgesia (PCA) and opioids for postoperative analgesia in children. In this study, we investigated the efficacy, usefulness and analgesic consumption of two different PCA programmes [bolus dose alone (BD) or bolus dose with background infusion (BD + BI)] to evaluate postoperative analgesia for children after emergency appendicectomy. Forty children, aged between 6 and 15 years and ASA class I or II, undergoing emergency appendicectomy were randomly allocated into two groups. The children were given a loading dose of pethidine 0.3 mg.kg-1 and 150 micro g.kg-1 bolus intravenously in group BD (n = 20) and pethidine 0.3 mg.kg-1 loading dose, 75 micro g.kg-1 bolus and 15 micro g.kg-1.h-1 background infusion in group BD + BI (n = 20). The lockout interval was 20 min in both groups. There were no significant differences in pain, sedation and nausea scores during the 24-h postoperative period between the groups (P > 0.05). Pethidine consumption was significantly lower in group BD + BI than that in group BD for the first 24-h period (P < 0.05). We demonstrated that both these PCA programmes were effective and reliable for postoperative pain relief in children. We believe that giving information about PCA to the children and their parents is useful during the preoperative period. However, the background infusion with lower bolus dose in PCA did not increase pethidine consumption.


Surgical protocols and outcome for the treatment of maxillofacial fractures in children: 9 years' experience.
Trauma and facial fractures in a population of children have been analysed in several studies mainly regarding their incidence and much less their treatment modalities. The aim of this study was to retrospectively analyse the treatment methods and outcome of facial fractures in children and young adolescents during the last decade and to discuss findings and propose treatment protocols. Patients of the Paediatric Maxillofacial department, treated for fractures of the facial skeleton were included in the study. Open reduction and osteosynthesis plate fixation (titanium and resorbable material) was the main treatment method with conservative treatment saved for selected cases. Titanium plates were removed after bone healing. Intermaxillary fixation (IMF) was not used regularly in mandibular fractures, with the exception of condylar fractures. 156 children and young adolescents with 208 fracture sites in total were treated. 139 fracture sites (66.8%) were treated with open reduction and 69 conservatively. The mandible was affected in 49.0% of the cases, the maxilla in 21.2% (both with the alveolar process fractures included), the zygomatic complex in 10.1%, the orbital walls in 9.6%. There were 38 alveolar process fractures. The results of the fracture treatment verified the usefulness of open reduction and plate fixation in children. There was no need for wire suspension and only occasional need for IMF. Closed reduction was selectively applied in condylar fractures and dento-alveolar trauma.


Review and analysis of the overlapping threats of carbapenem and polymyxin resistant E. coli and Klebsiella in Africa.
Carbapenem-resistant Enterobacterales are among the most serious antimicrobial resistance (AMR) threats. Emerging resistance to polymyxins raises the specter of untreatable infections. These resistant organisms have spread globally but, as indicated in WHO reports, the surveillance needed to identify and track them is insufficient, particularly in less resourced countries. This study employs comprehensive search strategies with data extraction, meta-analysis and mapping to help address gaps in the understanding of the risks of carbapenem and polymyxin resistance in the nations of Africa. Three comprehensive Boolean searches were constructed and utilized to query scientific and medical databases as well as grey literature sources through the end of 2019. Search results were screened to exclude irrelevant results and remaining studies were examined for relevant information regarding carbapenem and/or polymyxin(s) susceptibility and/or resistance amongst E. coli and Klebsiella isolates from humans. Such data and study characteristics were extracted and coded, and the resulting data was analyzed and geographically mapped. Our analysis yielded 1341 reports documenting carbapenem resistance in 40 of 54 nations. Resistance among E. coli was estimated as high (> 5%) in 3, moderate (1-5%) in 8 and low (< 1%) in 14 nations with at least 100 representative isolates from 2010 to 2019, while present in 9 others with insufficient isolates to support estimates. Carbapenem resistance was generally higher among Klebsiella: high in 10 nations, moderate in 6, low in 6, and present in 11 with insufficient isolates for estimates. While much less information was available concerning polymyxins, we found 341 reports from 33 of 54 nations, documenting resistance in 23. Resistance among E. coli was high in 2 nations, moderate in 1 and low in 6, while present in 10 with insufficient isolates for estimates. Among Klebsiella, resistance was low in 8 nations and present in 8 with insufficient isolates for estimates. The most widespread associated genotypes were, for carbapenems, blaOXA-48, blaNDM-1 and blaOXA-181 and, for polymyxins, mcr-1, mgrB, and phoPQ/pmrAB. Overlapping carbapenem and polymyxin resistance was documented in 23 nations. While numerous data gaps remain, these data show that significant carbapenem resistance is widespread in Africa and polymyxin resistance is also widely distributed, indicating the need to support robust AMR surveillance, antimicrobial stewardship and infection control in a manner that also addresses broader animal and environmental health dimensions.


Phenolic constituents with anti-inflammatory and cytotoxic activities from the rhizomes of Iris domestica.
Four undescribed flavonoid glucosides (iridins B-C, tectoridin A and ampelopsinin A); one undescribed phenolic glucoside (diplostephioside B); one undescribed phenolic compound (phenanthrenetriol A); and seventeen known compounds were isolated from the rhizomes of Iris domestica. The chemical structures of the undescribed compounds were established by spectroscopic/spectrometric data interpretation using HRESIMS, NMR, and ECD. Tectoridin A, nigricin A and naringenin exhibited anti-inflammatory activities with inhibition rates of 53.71%, 57.68% and 88.71%, respectively, against the NF-κB signaling pathway at a concentration of 10 μM. 4'-O-methylnyasol (10 μM) exhibited 84.91% antiproliferative activity against the K562 human leukemia cell line with an IC50 value of 4.20 μM.


Sequence of DNA replication in Macaca fuscata chromosomes: an outgroup for phylogenetic comparison between man and apes.
The relative replication times of every band in the standardized 300 band G-band idiogram of the chromosomes of the Japanese macaque are presented, and compared to the human sequence. Many chromosomes thought to be homologous between Macaca fuscata and man on the basis of standard chromosome banding and gene mapping show a conservation of the replication sequence. Other supposed chromosomal homologies between these two species show no good correspondence, and the replication sequence data suggest that these chromosomes have been subject to complex rearrangements. The replication sequence data also point to possible additional chromosomal homologies between man and M. fuscata. Asynchrony in replication time between homologues from the same cell may also be evolutionarily conserved, because these species share a number of asynchronous homologous bands. Replication band sequence data can provide significant information for comparative cytogenetics. However, usually only the full replication R- or G-band pattern has been used for interspecific comparisons. The dynamic sequence data presented here determine the replication time of every band in the karyotype, and provide a quantitatively and qualitatively more sensitive tool to characterize chromosomes. Such data could provide valuable new information on which to make phylogenetic reconstructions, and shed light on the relationship between chromosome change and evolutionary process. Finally, the M. fuscata replication sequence presented here will provide a necessary foundation for future comparisons between apes and man.


The application of CRISPR/Cas9 system in cervical carcinogenesis.
Integration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.


Bacterial type II toxin-antitoxin systems acting through post-translational modifications.
The post-translational modification (PTM) serves as an important molecular switch mechanism to modulate diverse biological functions in response to specific cues. Though more commonly found in eukaryotic cells, many PTMs have been identified and characterized in bacteria over the past decade, highlighting the importance of PTMs in regulating bacterial physiology. Several bacterial PTM enzymes have been characterized to function as the toxin component of type II TA systems, which consist of a toxin that inhibits cell growth and an antitoxin that protects the cell from poisoning by the toxin. While TA systems can be classified into seven types based on nature of the antitoxin and its activity, type II TA systems are perhaps the most studied among the different TA types and widely distributed in eubacteria and archaea. The type II toxins possessing PTM activities typically modify various cellular targets mostly associated with protein translation and DNA replication. This review mainly focuses on the enzymatic activities, target specificities, antitoxin neutralizing mechanisms of the different families of PTM toxins. We also proposed that TA systems can be conceptually viewed as molecular switches where the 'on' and 'off' state of the system is tightly controlled by antitoxins and discussed the perspective on toxins having other physiologically roles apart from growth inhibition by acting on the nonessential cellular targets.


The yield of chromosomal microarray testing for cases of abnormal fetal head circumference.
Chromosomal microarray analysis (CMA) is the method of choice for genetic work-up in cases of fetal malformations. We assessed the detection rate of CMA in cases of abnormal fetal head circumference (HC). The study cohort was based on 81 cases of amniocenteses performed throughout Israel for the indication of microcephaly (53) or macrocephaly (28), from January 2015 through December 2018. We retrieved data regarding the clinical background, parental HCs and work-up during the pregnancy from genetic counseling summaries and from patients' medical records. There was only one likely pathogenic CMA result (1.89%): a 400-kb microdeletion at 16p13.3 detected in a case of isolated microcephaly. No pathogenic results were found in the macrocephaly group. Most fetuses with microcephaly were female (87.8%), while the majority with macrocephaly were males (86.4%). The results imply that CMA analysis in pregnancies with microcephaly may carry a small yield compared to other indications. Regarding macrocephaly, our cohort was too small to draw conclusions. In light of the significant gender effect on the diagnosis of abnormal HC, standardization of fetal HC charts according to fetal gender may normalize cases that were categorized outside the normal range and may increase the yield of CMA for cases of abnormal HC.


Joint trajectory analysis of treated adolescents' alcohol use and symptoms over 1 year.
This study characterized treated adolescents' alcohol use and symptom trajectories over 1 year to describe the form of use trajectories and symptom trajectories, and the joint probability of membership in alcohol use and symptom trajectory groups. 109 teens (age 14-18, 66% male, 94% white), recruited from addictions treatment, with a lifetime DSM-IV alcohol diagnosis, reported on daily alcohol use and symptoms in monthly phone contacts using the Time Line Follow-Back method. A group-based modeling method jointly estimated trajectories of use and symptoms. Four alcohol use trajectories were identified: "Abstinent" (31%), Low (36%), Increasing (28%), and High Use (5%). Three alcohol symptom trajectories were identified: Very Low severity (44%), Mild (44%), and High severity (12%). The most frequent joint outcome was "Abstinent" and Very Low symptom severity (32%). Symptom severity was moderately related to alcohol use pattern over 1 year. Findings have implications for moving beyond relapse defined as a return to "any use" to consideration of treatment outcome in terms of a broader pattern of alcohol use and problems.


HLA antigens in patients with scabies.
Sixty patients with scabies were typed for thirty-three antigens of the HLA-A, -B and -C series. A significantly increased frequency was found for HLA-AII (28.3%), compared to healthy controls (10.4%). This deviation was only found in those of the patients without signs of atopic disease.


An Infrastructure to Provide Safer, Higher-Quality, and More Equitable Telehealth.
The rapid expansion and prompt widescale adoption of telehealth during the COVID-19 pandemic resulted in telehealth practice variations across health care settings and has implications for patient safety, health equity, and quality of care. Telehealth is part of the public health infrastructure, and health care stakeholders have an opportunity to strategically plan for telehealth expansion and sustainability in organizations as the pandemic wanes. A framework to guide organizational telehealth integration is needed that can support safe, accessible, and high-quality telehealth to patients regardless of social and/or economic status. The purpose of this article is to propose an innovative telehealth model, supported by systems theory, to address the complexity of telehealth implementation in health care organizations. A Donabedian approach is used to address quality. The telehealth model is an organizational infrastructure that outlines how policy and authority requirements, organization factors, provider competencies, and patient determinants of health influence safer, more equitable, higher-quality telehealth. The framework can guide leaders in building, redesigning, and measuring the impact of telehealth programs as health care shifts into a revolutionary technology era to meet the needs of diverse organizations and populations.


Diagnostic imaging in 2001 - a health economics perspective.
Factors contributing to the growth and diffusion of new imaging technologies are discussed. The benefits derived from implementing and using new technologies are carefully evaluated against the associated costs to both patients and service providers. The need to invest in early scientific assessment of a new imaging technology in order to prevent wasted acquisition and utilisation later on is highlighted. Such assessment might involve evaluating the ability of the technology to improve diagnosis, positively impact on treatment plans and, above all, improve health.


Identification of residues in the adult nicotinic acetylcholine receptor that confer selectivity for curariform antagonists.
We identify residues in the epsilon and delta subunits of the adult nicotinic acetylcholine receptor that give the alphaepsilon and alphadelta binding sites different affinities for the curariform antagonist dimethyl d-tubocurarine (DMT). By constructing epsilon-delta subunit chimeras, coexpressing them with complementary subunits, and measuring DMT binding, we identify two pairs of residues, Ileepsilon58/Hisdelta60 and Aspepsilon59/Aladelta61, responsible for DMT site selectivity in the adult receptor. The two determinants contribute approximately equally to the binding site and interact in contributing to the site. Exchange of these residues from one subunit to the other exchanges the affinities of the resulting binding sites. These determinants in the adult receptor are far from those that confer site selectivity in the fetal receptor; determinants in the fetal receptor are Ilegamma116/Valdelta118, Tyrgamma117/Thrdelta119, and Sergamma161/Lysdelta163. Thus, alternative residues confer DMT selectivity in fetal and adult acetylcholine receptors.


Reduction of liver glutathione peroxidase activity and deficiency of serum selenium in patients with hepatocellular carcinoma.
Twelve adults with hepatocellular carcinoma (HCC) and 8 individuals with histologically normal liver, were measured for serum selenium concentration and glutathione peroxidase (GSH-Px) of liver tissue. It was found a reduced serum selenium and liver GSH-Px in patients with HCC. Serum selenium concentration and the enzyme activity were positively correlated (p less than 0.01). The increased risk of carcinoma in selenium deficiency may be partially due to a reduced activity of GSH-Px, one of the most important scavenger enzymes of oxygen toxic radicals.


Immunity, aging, and geriatric depression.
Inflammatory processes are likely to play a causal role in geriatric depression. Geriatric depression occurs in the context of illnesses in which inflammatory processes are part of the pathogenesis. Both aging and depression are associated with immune responses, and the connectivity among mood-regulating structures may be modulated by inflammatory responses. Geriatric depression exacerbates the symptoms of comorbid disorders. Geriatric depression often occurs in persons exposed to chronic stress, a state precipitating geriatric depression and triggering proinflammatory responses. The successful treatment of comorbid conditions that increase central nervous system inflammatory responses has general health benefits and should be part of clinical practice.


Allocation plans for crisis triage: How well would they actually work?
COVID-19 has forced US state governments to create plans for rationing critical care resources that ensure the greatest population benefit. But a study by Jezmir and colleagues in this issue of Cell Reports Medicine raises doubts about whether these plans can distinguish those who would most benefit.


Plasmacytoma development in mice injected with silicone gels.
Silicone gels derived from commercially obtained implants induce plasmacytomas in 60-70% of highly susceptible BALB/cAn.DBA/2-Idh1-Pep3 congenic mice. In contrast, dimethylpolysiloxane (DMPS) silicone oils with viscosities of 5, 1000 and 12,500 cs fail to elicit these tumors. 1000 cs vinylmethylpolysiloxane is also inactive. Silicone gels, in contrast to the oils, induce a highly inflammatory silicone granuloma. Silicone gels contain chemical components not found in the oils. The chemical component responsible for inducing the permissive environment for plasmacytoma formation has not yet been identified. Silicone gels are well tolerated for long periods of time in mice without adverse effects other than plasmacytoma formation. The response to different gel preparations varies; some are associated with relatively rapid formation of plasmacytomas resembling that seen with pristane, while in others the plasmacytoma formation is extended nearly over a two year period.


Pancreaticoduodenectomy for benign disease.
Surgeons are often called upon to perform pancreaticoduodenectomy for either suspicion of malignancy or symptoms due to benign disease. Perioperative morbidity and mortality following pancreaticoduodenectomy have decreased markedly over the last 2 decades. In response, many surgical centers advocate expanding the indications for pancreaticoduodenectomy to include lesions other than periampullary carcinoma. A retrospective review of medical records for 108 patients undergoing pancreaticoduodenectomy for benign disease at The Johns Hopkins Medical Institutions over 100 months was completed. The subset of patients with a histopathologic diagnosis of chronic pancreatitis was identified and compared with patients undergoing pancreaticoduodenectomy for other benign conditions. The mortality rate for the present series was less than 1%. Perioperative complications, the majority of which were self-limited, occurred in 51% of patients. The most common complication was delayed gastric emptying. Pancreatic anastamotic leak occurred in 18% of patients and developed significantly more frequently in patients with benign diseases other than chronic pancreatitis (31% versus 8%, P < 0.05). Among appropriately selected patients, the rates of perioperative mortality and serious morbidity are low, and concerns about mortality and morbidity should not prevent an aggressive approach to surgical resection in patients with benign disease.


Introgression of dual abiotic stress tolerance QTLs (Saltol QTL and Sub1 gene) into Rice (Oryza sativa L.) variety Aiswarya through marker assisted backcross breeding.
Salinity and submergence are two very prominent abiotic stress conditions affecting rice yield adversely in the coastal agro ecosystem. Marker Assisted Backcross Breeding (MABB) is an efficient and fast track molecular tool to incorporate a desired stress tolerant QTL/gene into an improved cultivar. The present study was carried out for the introgression of Saltol QTL responsible for salinity tolerance and Sub1 gene responsible for submergence tolerance into the high yielding rice variety Aiswarya independently through MABB. Final objective of the study is to develop dual stress tolerant (tolerance to salinity and submergence) Aiswarya rice variety by pyramiding the both target QTLs introgressed BC2F2 progenies having maximum background homozygosity. The donors of Saltol QTL and Sub1 gene used in the present study were FL478 and Swarna Sub1, respectively. Based on the background genome analysis of the introgressed plants, the plants with > 85-90% background similarity were selected for pyramiding of Saltol QTL and Sub1 gene into the elite background of rice variety Aiswarya. Those selected introgressed lines with Saltol QTL and Sub1 gene will be again crossed to pyramid both Saltol QTL and Sub1 gene into the rice variety Aiswarya. Such a mega rice variety pyramided with dual stress tolerant QTLs is the expected outcome of this study and can be recommended for cultivation in the flood prone saline coastal agroecosystem.


A Comparative Analysis of Surface Characteristics of Enamel after Conventional Acid Etching and Er,Cr:YSSG Laser Irradiation.
To evaluate the influence of Erbium, Chromium:Yttrium-Scandium-Gallium-Garnet (Er,Cr:YSGG) laser irradiation (2W 15Hz, 2W 25Hz) on Penetration Depth, Surface Roughness, Surface Morphology and Etching Pattern of enamel and to compare it with conventional acid etching. Sixty sound human premolars extracted for orthodontic reasons were used for this study. Penetration Depth and Surface Roughness between Acid Etched and Laser Etched Enamel were evaluated using Non-contact 3D- Profilometer .Surface Morphology and the Etching Pattern were evaluated using Field Emission - Scanning Electron Microscope. On comparing the maximum depth and surface roughness values among all the three groups, highest was found in the acid-etched group, followed by the 2W 15Hz laser-etched group and the least was with the 2W 25Hz laser-etched group. The laser etching of enamel surface with an Er,Cr:YSGG laser system showed Type 3 etching pattern, whereas acid etched surface showed Type 1 etching pattern as described by Silverstone (1974). Er,Cr:YSGG laser irradiation produces favourable etching pattern and micro-irregularities that are suitable for resin penetration. Moreover, due to its decreased surface roughness and penetration depth, laser etching can significantly decrease the probability of formation of white spot lesions which is proved to be the potential disadvantage of conventional acid etching. Hence, laser etching can be preferred over the conventional phosphoric acid etching for orthodontic bonding. Key words:Laser, Er,Cr:YSGG, Surface Roughness, Etching Pattern,Penetration Depth,SEM, Laboratory Research, Acid etching.


Preterm birth in the African-American community.
Preterm births account for a substantial portion of infant mortality, the major difference in mortality between African-American and white births in the United States, and the key reason that US infant mortality exceeds that of other developed nations. Although preterm birth rates are higher in the African-American community for certain known reasons (proportionately more unwanted conceptions, poorer nutrition, less sufficient prenatal care, and stress-associated behavioral risks), most of the excess risk for preterm delivery remains unexplained. Because preterm delivery is poorly understood in general, prevention strategies are limited. Future research directions should explore contextual and social conditions that might be altered to reduce preterm births in the African-American community.


Identification of the novel HLA-DQA1*01:04:04 allele by next-generation sequencing.
HLA-DQA1*01:04:04 differs from HLA-DQA1*01:04:01:01 by a single nucleotide substitution at position 225 C > T.


The Nottingham study of neurotic disorder: predictors of 12 year costs.
To examine the relationship between clinical, demographic and socio-economic characteristics and the long-term costs of a cohort of neurotic patients. Analysis of the costs of a cohort of 210 people entered in the Nottingham study of neurotic disorders, a randomized controlled evaluation of five treatments for neurotic disorders. Service use data were collected at 5 and 12 years after study entry. Multiple regression analyses were conducted. The total cost per patient over the 12-year follow-up period was calculated to be $11,940 (SD $15,520) ( pound7450, SD pound9690). Higher costs were significantly associated with the presence of general neurotic syndrome, an initial diagnosis of dysthymia and a recurrent episode of illness. The total costs of care for a range of neurotic disorders are broadly comparable with other estimates of costs reported in the literature for similar populations. Those responsible for higher costs in the longer-term have comorbid anxiety, depressive and personality disorders.


Papers on fishes of Asia, including those presented at international conferences of the Asian Society of Ichthyologists in Taipei, Taiwan in 2016, and in Ho Chi Minh City, Vietnam in 2017 (Cover Copytight page).
(Cover Copytight page).


Phagocytic activities in neonatal monocytes.
Monocytes play an essential role in cellular host defense as circulating phagocytes, as well as precursors of macrophages. We investigated the principal phagocytic activities in monocytes from cord blood of term infants by analysing adherence, random migration, chemotaxis, bactericidal activity, phagocytosis-associated chemiluminescence, production of superoxide anion (O-2) and generation of hydrogen peroxide (H2O2). All phagocytic functions of monocytes from neonates were shown quantitatively to be comparable to those of cells from healthy adult volunteers. The increased susceptibility of the human neonate to serious systemic infections cannot be related to an abnormality in monocyte function.


Efficacy of novel histone deacetylase inhibitor, AR42, in a mouse model of, human T-lymphotropic virus type 1 adult T cell lymphoma.
Human T-lymphotropic virus type 1 (HTLV-1) causes a variety of forms of adult T-cell leukemia/lymphoma (ATL), a refractory CD4+/CD25+ T-cell malignancy. Novel approaches to treat ATL patients are required due to the resistance of ATL to conventional chemotherapies. Histone deacetylase inhibitors (HDACi), which induce histone hyperacetylation leading to chromatin remodeling and reactivation of transcriptionally repressed genes have shown efficacy against a variety of cancers. Herein, we tested if valproic acid and the novel orally bioavailable HDACi, AR-42 reduced the proliferation of ATL cell lines by promoting apoptosis and histone hyperacetylation. Both compounds were cytotoxic and elicited a dose dependent increase in cytochrome C and cleaved Poly (ADP-ribose) polymerase (PARP) indicating the induction of cell death by apoptosis and promoted acetylation of histone H3 in both MT-2 and C8166 cell lines. We then evaluated the effects of AR-42, for survival in an ATL NOD/SCID mouse model. A dietary formulation of AR-42 prolonged survival of ATL engrafted mice compared to controls. Our data provide new directions for the treatment of ATL and support the further development of AR-42 against HTLV-1-associated lymphoid malignancies.


FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors.
Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial prefrontal cortex (mPFC) leads to reduced PVI excitability, impaired mPFC gamma oscillation, and SCZ-like behaviors. PVI-specific translational profiling reveals that FXR1 regulates the expression of Cacna1h/Cav3.2 a T-type calcium channel implicated in autism and epilepsy. Inhibition of Cav3.2 in PVIs of mPFC phenocopies whereas elevation of Cav3.2 in PVIs of mPFC rescues behavioral deficits resulted from FXR1 deficiency. Stimulation of PVIs using a gamma oscillation-enhancing light flicker rescues behavioral abnormalities caused by FXR1 deficiency in PVIs. This work unveils the function of a newly identified SCZ risk gene in SCZ-relevant neurons and identifies a therapeutic target and a potential noninvasive treatment for psychiatric disorders.


Oncologic efficacy is not compromised, and may be improved with minimally invasive esophagectomy.
Major morbidity and mortality rates continue to be high in large series of transthoracic esophagectomies. Minimally invasive approaches are being increasingly used. We compare our growing series of minimally invasive (combined thoracoscopic and laparoscopic) esophagectomies (MIEs) with a series of open transthoracic esophagectomies. We identified 65 patients who underwent an MIE with thoracoscopy/laparotomy (n = 11), Ivor Lewis (n = 2), or 3-hole approach (n = 52). These patients were compared with 53 patients who underwent open Ivor-Lewis esophagectomy (n = 15) or 3-hole esophagectomy (n = 38) over the past 10 years. The MIE and open groups were similar regarding gender and average age. The majority of patients in the open group underwent neoadjuvant chemoradiation therapy (81%); a significantly smaller (43%) number of patients in the MIE group underwent neoadjuvant therapy (p < 0.0001). Regarding oncologic efficacy, 97% and 94% of patients in both groups underwent R0 resections. Patients undergoing MIE had a significant increase in the number of harvested lymph nodes (median 20 vs 9; p < 0.0001). Length of stay was significantly decreased in patients who underwent MIE (8.5 days vs 16 days; p = 0.002). Finally, there were significantly fewer serious complications (grades 3-5) in the MIE group (19% vs 48%; p = 0.0008). In this initial report of a single-institution series of MIE, we demonstrate that oncologic efficacy is not compromised and may actually be improved with a significantly increased number of harvested LNs. We also demonstrate that this approach is associated with fewer serious complications and a significant decrease in the length of postoperative hospital stay.


Awake spinal anesthesia facilitates spine surgery in poor surgical candidates: A case series.
Annually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA. With this in mind, the authors set out to summarize the outcomes of a series of highly comorbid patients who received surgery under SA. Case logs of a single surgeon were reviewed, and patients undergoing spine surgery under SA were identified. Within this group, patients were identified with relative contraindications to GA, such as advanced age and medical comorbidities. For these patients, for whom surgery was facilitated by SA, the medical records were consulted to report demographic information and patient outcomes. Ten highly comorbid patients were identified who received lumbar spine surgery for DSD under SA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as heart disease. The cohort had a mean age of 75.5 and a mean American Society of Anesthesiologists Physical Status (ASA-PS) score of 3.1. The patients were predicted to have a 2.74-fold increase of serious complications compared to the average patient. There were no adverse events. For patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.


What conditions lead to euthanasia in dogs?
Georgina Mills reports on new research that looks into the risk factors for euthanasing dogs.


Detection of matrix metalloproteinase activity in human pancreatic cancer.
Destruction of the basement membrane (BM) is mandatory for tumor spread, and matrix metalloproteinases (MMPs) are known to be implicated in colon cancer invasion and metastasis by digesting type IV collagen, a main component of the BM. The current study analyzed the expression of MMP-2 and MMP-9 in pancreatic cancer tissues. Frozen specimens of pancreatic cancer (n = 10), a liver metastatic nodule from pancreatic cancer (n = 1), and normal pancreas (n = 3) were homogenized and analyzed by zymography. The activated form of MMP-9 (82 kDa) was detected in all of the normal and malignant tissues, while the activated form of MMP-2 (62 kDa) was detected in all of the pancreatic cancers and its metastatic tissue, but not in the normal pancreatic tissues. These results indicate that expression of the activated form of MMP-2 may be specific to pancreatic cancer, while that of MMP-9 may be unrelated to it.


Diphenhydramine prevents the haemodynamic changes of cimetidine in ICU patients.
Cimetidine, a histamine 2 (H2) antagonist, produces a decrease in arterial pressure due to vasodilatation, especially in critically ill patients. This may be because cimetidine acts as a histamine agonist. We, therefore, investigated the effects of the histamine 1(H1) receptor antagonist, diphenhydramine, on the haemodynamic changes observed after cimetidine in ICU patients. Each patient was studied on two separate days. In a random fashion, they received cimetidine 200 mg iv on one day, and on the other, a pretreatment of diphenhydramine 40 mg iv with cimetidine 200 mg iv. In the non-pretreatment group, mean arterial pressure (MAP) decreased from 107.4 +/- 8.4 mmHg to 86.7 +/- 11.4 mmHg (P less than 0.01) two minutes after cimetidine. Also, systemic vascular resistance (SVR) decreased during the eight-minute observation period (P less than 0.01). In contrast, in the pretreatment group, little haemodynamic change was seen. We conclude that an H1 antagonist may be useful in preventing hypotension caused by iv cimetidine, since the vasodilating activity of cimetidine is mediated, in part, through the H1 receptor.


Epidemiology of Mycoplasma pneumoniae infection in the United Kingdom: an analysis of reports to the Public Health Laboratory Service of England and Wales.
Infection with Mycoplasma pneumoniae appears to follow a cyclic pattern in the United Kindom, with periods of increased prevalence lasting about two years. Outbreaks occurred in 1971-1972 and 1974-75, and probably also in 1967-68. Infection confirmed by laboratory tests appeared to be commonest in older children, especially those aged 5-14, and least common in adults over 65 years of age. Lower respiratory tract infection was the clinical feature most frequently reported.


Nitrogen-doped hydrochar prepared by biomass and nitrogen-containing wastewater for dye adsorption: Effect of nitrogen source in wastewater on the adsorption performance of hydrochar.
Dye wastewater has become one of the main risk sources of environmental pollution due to its high toxicity and difficulty in degradation. Hydrochar prepared by hydrothermal carbonization (HTC) of biomass has abundant surface oxygen-containing functional groups, and therefore is used as an adsorbent to remove water pollutants. The adsorption performance of hydrochar can be enhanced after improving its surface characteristics through nitrogen-doping (N-doping). In this study, wastewater rich in nitrogen sources such as urea, melamine and ammonium chloride were selected as the water source for the preparation of HTC feedstock. The N atoms were doped in the hydrochar with a content of 3.87%-5.70%, and mainly in the form of pyridinic-N, pyrrolic-N and graphitic-N, which changed the acidity and basicity of the hydrochar surface. The N-doped hydrochar adsorbed methylene blue (MB) and congo red (CR) in wastewater through pore filling, Lewis acid-base interaction, hydrogen bond, and π-π interaction, and the maximum adsorption capacities of those were obtained with 57.52 mg/g and 62.19 mg/g, respectively. However, the adsorption performance of N-doped hydrochar was considerably affected by the acid-base property of the wastewater. In a basic environment, the surface carboxyl of the hydrochar exhibited a high negative charge and thus an enhanced electrostatic interaction with MB. Whereas, the hydrochar surface was positively charged in an acid environment by binding H+, resulting in an enhanced electrostatic interaction with CR. Therefore, the adsorption efficiency of MB and CR by N-doped hydrochar can be tuned by adjusting the nitrogen source and the pH of the wastewater.


Transcatheter arterial chemoembolization (TACE) in the treatment of unresectable liver cancer.
Basis, techniques, and recent strategies and results of interventional treatments for hepatoma were reviewed. The basic experimental researches indispensable to justify clinical technique and dosage have been accomplished. A total of 1310 unresectable cases underwent transcatheter arterial chemoembolization (TACE) and/or related therapies. The related therapies are several modified or strengthened TACE such as Lipiodol-TACE and subsegmental TACE. The therapies for unembolizable cases are balloon occluded arterial infusion, Lipiodol-SMANCS infusion and percutaneous direct injection chemotherapy, that reinforces the effect of TACE. As for the resectable cases, postoperative TACE was proved to be beneficial because it increased survival rates; however, preoperative TACE was not beneficial. The TACE and related interventional radiologic therapies for the hepatoma can be an equal or superior therapy by virtue of targeting chemotherapy.


National contributions to climate change due to historical emissions of carbon dioxide, methane, and nitrous oxide since 1850.
Anthropogenic emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) have made significant contributions to global warming since the pre-industrial period and are therefore targeted in international climate policy. There is substantial interest in tracking and apportioning national contributions to climate change and informing equitable commitments to decarbonisation. Here, we introduce a new dataset of national contributions to global warming caused by historical emissions of carbon dioxide, methane, and nitrous oxide during the years 1851-2021, which are consistent with the latest findings of the IPCC. We calculate the global mean surface temperature response to historical emissions of the three gases, including recent refinements which account for the short atmospheric lifetime of CH4. We report national contributions to global warming resulting from emissions of each gas, including a disaggregation to fossil and land use sectors. This dataset will be updated annually as national emissions datasets are updated.


Neural development. Spinning skin into neurons.
Basic helix--loop--helix proteins are transcriptional regulations with important roles in myogenesis and neurogenesis. One such protein, NeuroD, has an impressive ability to promote ectopic neuronal differentiation in xenopus.


Controlling phase formation in solids: rational synthesis of phase separated Co@Fe2O3 heteroparticles and CoFe2O4 nanoparticles.
A wet chemical approach from organometallic reactants allowed the targeted synthesis of Co@Fe(2)O(3) heterodimer and CoFe(2)O(4) ferrite nanoparticles. They display magnetic properties that are useful for magnetic MRI detection.


Exposure to urban stressors and free testosterone plasma values.
The chemical agents present in the environment, such as traffic pollutants, may affect male fertility. Traffic policemen are daily exposed to traffic pollutants. The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in free testosterone plasma values in male traffic policemen versus administrative staff of Municipal Police of a big Italian city. Both groups were divided into two subgroups based on age (first group: 30-40 years; second group: 41-50 years) to assess whether age could affect laboratory results of free testosterone plasma levels in traffic policemen versus controls. The characterization of exposure to urban pollutants for traffic policemen was assessed using the concentrations of pollutants monitored in fixed stations. A total of 220 subjects were studied: 110 traffic policemen and 110 controls, after excluding subjects with main confounding factors. Mean free testosterone values were significantly lower in traffic policemen than in controls (P < 0.001). Such statistical reduction persisted stratifying the mean testosterone values for classes of age (30-40 and 41-50 year) of workers (respectively P < 0.001 and P < 0.001). The distribution into classes of testosterone values in traffic policemen and in controls was significant (P < 0.001), and this result persisted after the stratification for classes of age of workers (30-40 year: P < 0.001) (41-50 year: P < 0.001). According to data in literature, free testosterone plasma levels could be used as an early biological marker, to be employed in occupational sets, valuable for the group, even before the onset of values out of range and of fertility disorders.


Unlocking the potential of induced pluripotent stem cells for neonatal disease modeling and drug development.
Neonatal lung and heart diseases, albeit rare, can result in poor quality of life, often require long-term management and/or organ transplantation. For example, Congenital Heart Disease (CHD) is one of the most common type of congenital disabilities, affecting nearly 1% of the newborns, and has complex and multifactorial causes, including genetic predisposition and environmental influences. To develop new strategies for heart and lung regeneration in CHD and neonatal lung disease, human induced pluripotent stem cells (hiPSCs) provide a unique and personalized platform for future cell replacement therapy and high-throughput drug screening. Additionally, given the differentiation potential of iPSCs, cardiac cell types such as cardiomyocytes, endothelial cells, and fibroblasts and lung cell types such Type II alveolar epithelial cells can be derived in a dish to study the fundamental pathology during disease progression. In this review, we discuss the applications of hiPSCs in understanding the molecular mechanisms and cellular phenotypes of CHD (e.g., structural heart defect, congenital valve disease, and congenital channelopathies) and congenital lung diseases, such as surfactant deficiencies and Brain-Lung-Thyroid syndrome. We also provide future directions for generating mature cell types from iPSCs, and more complex hiPSC-based systems using three-dimensional (3D) organoids and tissue-engineering. With these potential advancements, the promise that hiPSCs will deliver new CHD and neonatal lung disease treatments may soon be fulfilled.


Association of neck circumference with insulin resistance-related factors.
Overall and central obesity are associated with disorders in lipid and glucose metabolism, insulin resistance, hypertension, atherosclerosis and type 2 diabetes. Waist circumference and abdominal sagittal diameter have been suggested as the best simple anthropometric indexes of abdominal visceral fat accumulation. The aim of the present study was to test the association of neck circumference with abdominal and general obesity as well as with insulin resistance related factors. Neck circumference was measured in addition to the traditional anthropometric measures and blood lipids, insulin and glucose concentrations and blood pressure. The prevalence rates of disorders in lipid or glucose metabolism and high fasting insulin concentrations were highest in the highest quintiles of all the anthropometric measures. We conclude that neck circumference is associated with the metabolic disorders related to insulin resistance. The measurement of neck circumference could be useful in clinical screening for persons at an enhanced risk for insulin resistance.