Proteomic composition and immunomodulatory properties of urinary bladder matrix scaffolds in homeostasis and injury.
Urinary bladder matrix (UBM) is used clinically for management of wounds and reinforcement of surgical soft tissue repair, among other applications. UBM consists of the lamina propria and basal lamina of the porcine urinary bladder, and is decellularized as part of the process to manufacture the medical device. UBM is composed mainly of Collagen I, but also contains a wide variety of fibrillar and basement membrane collagens, glycoproteins, proteoglycans and ECM-associated factors. Upon application of the biomaterial in a traumatic or non-traumatic setting in a mouse model, there is a cascade of immune cells that respond to the damaged tissue and biomaterial. Here, through the use of multicolor flow cytometry, we describe the various cells that infiltrate the UBM scaffold in a subcutaneous and volumetric muscle injury model. A wide variety of immune cells are found in the UBM scaffold immune microenvironment (SIM) including F4/80+ macrophages, CD11c+ dendritic cells, CD3+ T cells and CD19+ B cells. A systemic IL-4 upregulation and a local M2-macrophage response were observed in the proximity of the implanted UBM. The recruitment and activation of these cells is dependent upon signals from the scaffold and communication between the different cell types present.


Molecular definition of interstitial deletions of chromosome 13 in leukemic cells.
Three patients with leukemia and one with a myeloproliferative disorder carried an interstitial deletion of chromosome 13, del(13)(q12q14), in leukemic cells. Proximal and distal breakpoints of the deleted segment were characterized by using DNA restriction fragment length polymorphisms of chromosome 13 supplemented by quantitative densitometry of hybridization signals to determine the copy number of individual loci. Both proximal and distal breakpoints varied between patients, and it is unlikely that a significant hybrid gene was formed by rejoining at the breakpoint junctions. The retinoblastoma gene was encompassed by the deleted segment in all four patients.


Sleep in athletes and the effects of Ramadan.
Sleep is now considered as a new frontier in performance enhancement. This article presents background content on sleep function, sleep needs and methods of sleep investigation along with data on the potential effects of Ramadan fasting on sleep in normal individuals and athletes. Accumulated sleep loss has negative impacts on cognitive function, mood, daytime sleepiness and performance. Sleep studies in athletes fasting during Ramadan are very rare. Most of them have demonstrated that during this month, sleep duration decreased and sleep timing shifted. But the direct relation between sleep changes and performance during Ramadan is not yet elucidated. Objective sleep patterns can be investigated using polysomnography, actigraphy, and standardised questionnaires and recorded in daily journals or sleep logs. The available data on sleep indicate that team doctors and coaches should consider planning sleep schedule and napping; implementing educational programmes focusing on the need for healthy sleep; and consider routine screening for sleep loss in athletes of all age groups and genders.


Synthetic compound libraries displayed on the surface of encoded bacteriophage.
We describe a technology for attaching libraries of synthetic compounds to coat proteins of bacteriophage particles such that the identity of the chemical structure is encoded in the genome of the phage, analogous to peptides displayed on phage surfaces by conventional phage-display techniques. This format allows a library of synthetic compounds to be screened very efficiently as a single pool. Encoded phage serve as extremely robust reporters of the presence of each compound, providing exquisite sensitivity for identification of active compounds engaged in complex biological processes such as receptor-mediated endocytosis and transcytosis. To evaluate this approach, we constructed a library of 980 analogs of folic acid displayed on T7 phage, and demonstrated rapid identification of compounds that bind to folate receptor and direct endocytosis of associated phage particles into cells that express the targeted receptor.


[Punish or cherish: p53, metabolism and tumor suppression].
The p53 gene is essential for tumor suppression, but how it does so remains unclear. Upon genotoxic or oncogenic stresses, increased p53 activity induces transient cell cycle arrest, senescence or apoptosis, the three cornerstones of the so-called triumvirate. Accordingly, it has long been thought that p53 suppresses tumorigenesis by somehow counteracting cell proliferation or survival. However, several recently described genetically modified mice indicate that p53 can suppress tumorigenesis without triggering these three responses. Rather, as an important mechanism for tumor suppression, these mutant mice point to the ability of p53 to prevent the Warburg effect, that is to dampen glycolysis and foster mitochondrial respiration. Interestingly, these metabolic functions of p53 rely, in part, on its "unstressed" (basal) expression, a feature shared by its mechanistically linked anti-oxydant function. Together, these "conservative" activities of p53 may prevent tumor initiation by promoting and maintaining a normal oxidative metabolism and hence underly the "daily" tumor suppression by p53 in most cells. Conversely, destructive activities elicited by high p53 levels and leading to senescence or apoptosis provide a shield against partially or overtly transformed cells. This last situation, although relatively infrequent throughout life, is usual in experimental settings, which could explain the disproportionally high number of data implicating the triumvirate in tumor suppression by p53.


An evidence-based analysis of simultaneous pancreas-kidney and pancreas transplantation alone.
While pancreas transplantation has evolved within two decades from a frustrating and poorly-accepted therapeutic option to a highly successful procedure, the respective benefits of the successive surgical and immunosuppressive developments have remained unclear. The aim of this study was to determine using an evidence-based methodology, which novel approaches have contributed to the current results and whether pancreas transplantation is cost-effective. Out of 2481 articles, 102 analyzed either surgical or immunosuppressive aspects of pancreas transplantation. Urological complications were more frequent in bladder over enteric drainage (range: 62-63% vs. 12-20%, p = 0.0001), but without significant difference in patient or graft survival. Portal drainage was associated with a trend toward fewer complications and better hyperinsulinemia control over systemic drainage in retrospective studies. Immunosuppression combining induction therapy, a calcineurin inhibitor, mycophenolate mophetil (MMF) and corticosteroids were associated with a 40% decreased incidence of rejection (p = 0.01) and an increase in graft survival above 90% at 1 year (p < 0.05). Pancreas transplantation is highly cost-effective compared to conservative alternatives. We conclude that despite a paucity of large studies, enteric drainage should be recommended but the benefits of portal venous drainage remain debated. Quadruple immunosuppression protocols including induction therapy should be the standard regimen.


EFFECT OF A SHORT PERIOD WHOLE BODY VIBRATION WITH 10 HZ ON BLOOD BIOMARKERS IN WISTAR RATS.
Exposure to whole body vibration exercises (WBVE), besides some biological effects, causes alterations in the concentration of some blood biomarkers. The aim of this study is to evaluate the action of vibration (10 Hz) of WBVE on the concentration of blood biomarkers in Wistar rats. Wistar rats were divided in 2 groups. The experimental group (EG) was subjected to vibrations of 10Hz (one min per day, one week, total time of seven min), while the control group (CG) has not experienced vibration. Samples of whole blood were drawn for biochemical analysis of the concentration of total cholesterol, triglycerides, HDL, LDL, VLDL, glucose, CPK, albumin, alkaline phosphates, TGP, TGO, γGT, lipase, amylase, urea and creatinine. White blood cell count and a platelet-hemogram were also performed. Significant (p<0.05) increase in TGP, TGO and white blood cells and decrease in LDL concentration was found after exposure of 10Hz mechanical vibration. Although these findings were obtained with rats, they might contribute to try to understand better these mechanisms that occur following exposure to a frequency of 10Hz.


New earthworm species of the genus Amynthas from Hainan Island, China (Megascolecidae, Clitellata).
Three new species of earthworms belonging to the genus Amynthas are described from Hainan Island, China. They are named Amynthas wenchangensis sp. nov., Amynthas accessorius sp. nov., and Amynthas eumorphus sp. nov. A. wenchangensis sp. nov. keys to the Amynthas morrisi-group; it has several small genital papillae in the male pore region and a degenerated prostate. A. accessorius sp. nov. keys to the Amynthas hawayanus-group and has completely degenerated prostates and two large accessory glands. A. eumorphus sp. nov. keys to the Amynthas sieboldi-group.


Interplay of RNA elements in the dengue virus 5' and 3' ends required for viral RNA replication.
Dengue virus (DENV) is a member of the Flavivirus genus of positive-sense RNA viruses. DENV RNA replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5' and 3' ends, designated 5' and 3' cyclization sequences (5'-3' CS) and the 5' and 3' upstream of AUG region (5'-3' UAR). Here, we demonstrate that another stretch of six nucleotides in the 5' end is involved in DENV replication and possibly genome cyclization. This new sequence is located downstream of the AUG, designated the 5' downstream AUG region (5' DAR); the motif predicted to be complementary in the 3' end is termed the 3' DAR. In addition to the UAR, CS and DAR motifs, two other RNA elements are located at the 5' end of the viral RNA: the 5' stem-loop A (5' SLA) interacts with the viral RNA-dependent RNA polymerase and promotes RNA synthesis, and a stem-loop in the coding region named cHP is involved in translation start site selection as well as RNA replication. We analyzed the interplay of these 5' RNA elements in relation to RNA replication, and our data indicate that two separate functional units are formed; one consists of the SLA, and the other includes the UAR, DAR, cHP, and CS elements. The SLA must be located at the 5' end of the genome, whereas the position of the second unit is more flexible. We also show that the UAR, DAR, cHP, and CS must act in concert and therefore likely function together to form the tertiary RNA structure of the circularized DENV genome.


ArmA and RmtB Were the Predominant 16S RMTase Genes Responsible for Aminoglycoside-resistant Isolates in Korea.
Pathogenic gram-negatives that produce 16S ribosomal RNA methyltransferases (16S RMTases) have already been distributed all over the world. To investigate the predominance of aminoglycoside resistance associated with 16S RMTases in Korea, we collected a total of 222 amikacin resistant Gram-negative clinical isolates from patient specimens between 1999 and 2015 from three hospital banks across Korea. ArmA and rmtB were the predominant 16S RMTase genes responsible for aminoglycoside-resistant isolates circulating in Korean community settings although only one rmtA-producing isolate was detected in 2006.


Cervical cancer screening programs for female sex workers: a scoping review.
Cervical cancer (CC) is the fourth most common neoplasia affecting women worldwide. Female sex workers (FSWs) are among those at highest risk of developing and succumbing to CC. Yet, they are often overlooked in CC screening programs and have limited access to CC healthcare globally. The development of CC screening programs for this high-risk target population is necessary to reduce the global burden of this disease and to reach the World Health Organization's objective of accelerating the elimination of CC. This review summarizes findings on CC screening programs for FSWs that have been implemented worldwide, and assesses their effectiveness and sustainability. A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A literature search was performed on PubMed, Swisscovery, and Google Scholar for studies describing and assessing CC screening programs for FSWs. In addition, targeted searching online Non-Governmental and International Organizations websites identified grey literature. A single reviewer screened titles and abstracts, and extracted data from the research findings. The search identified 13 articles published from 1989 to 2021. All implemented programs successfully reached FSWs and provided them with CC screening during the study period. The most effective and sustainable strategies were the Screen and Treat approach, introducing CC screening into existing STI services in drop-in or outreach clinics, HPV-DNA self-sampling, and integrating sex-workers-specific services in public health facilities. Follow-up was deemed the main challenge in providing and enhancing CC healthcare to FSWs with rates of loss to follow-up ranging from 35 to 60%. FSWs are often omitted in national CC screening programs. The further development and improvement of CC healthcare, including follow-up systems, for this high-priority target population are imperative.


[The comparison of preemptive analgesic efficacy between short-acting ketamine and long-acting parecoxib].
Objective: To compare the analgesic efficacy between preoperative single-dose ketamine, a short-acting medicine and parecoxib, a long-acting medicine for reducing analgesic consumption in the first 24 h after-operation. Methods: Eighty-one patients from Beijing Chaoyang Hospital undergoing laparoscopic uterus surgery between April and December 2015 were randomly divided into three groups: control group (group C), ketamine group (group K) and parecoxib sodium group (group P). All patients were anesthetized with general anesthesia and received sufentanil-based patient-controlled intravenous analgesia (PCIA). After induction and 10 min before incision, patients in group K, P and C were injected with intravenous 0.5 mg/kg ketamine, 40 mg parecoxib and 2 ml normal saline, respectively. The primary outcome was sufentanil consumption within 1 h and 24 h after surgery. Other outcomes included the visual analog scale (VAS) pain score at 0, 15, 30, 45min and 1, 2, 4, 8, 24 h after surgery, PCIA effective trigger times, and adverse reactions. Results: The postoperative sufentanil consumptions within 1 h in group K and P were(4.420±1.836)μg and (2.878±1.984)μg, respectively, and consumptions within 24 h were(28.200±3.712)μg and (25.511±4.037)μg, respectively, which were significantly less than that in group C with (6.144±2.346)μg within 1 h and (31.505±7.042)μg within 24 h (F=15.360, 8.406, all P<0.05). Patients in group P needed less sufentanil than group K in 1 h after surgery (P<0.05), however, the difference was not statistically significant in 24 h(P>0.05). The PCIA trigger times were 2(3.75) in group C, 0(1.50) in group K, and 0(1.00) in group P. Group K and P had less PCIA trigger times compared to group C (all P<0.05). Compared to group C, group K and P had lower VAS scores at 0, 15, 30 min after surgery and group P had lower VAS scores at 1, 15, 30, 45 min, 2 h after surgery, respectively (all P<0.05). There were no differences between groups in the incidence of any adverse effects(all P>0.05). Conclusion: A single injection of short-acting ketamine before laparoscopic uterus surgery, has the same efficacy as long-acting parecoxib for opioid-sparing effect in the first 24 h after-operation. However, parecoxib has better analgesic effect in the early postoperative period.


Hemolytic and antifungal activity of liposome-entrapped amphotericin B prepared by the precipitation method.
A new method of preparing liposomes containing amphotericin B (AmB) was developed with the purpose of reducing the toxicity of AmB without causing a loss in its antifungal activity. The procedure involved the precipitation of AmB and egg phosphatidylcholine (PC) in phosphate buffered saline (PBS, pH 7.4) or tris buffered saline (TBS, pH 7.4) by evaporating methanol and chloroform, which had been previously mixed in the buffer solution, at 4 degrees C and 600 mm Hg. The in vitro toxicity of the precipitated liposomes containing 3, 6, 9, 12, and 15 wt% AmB was compared with that of the film-swollen liposomes containing the equivalent contents of the drug. The hemolytic ability of the precipitated liposomes at 37 degrees C was 50.3% at maximum of the film-swollen liposomes at a dose of 30 micrograms AmB/ml, as measured after 17-hr incubation. The significant reduction in the hemolysis effect may in fact be attributed to the reduced rate of drug release from the precipitated liposomes. The precipitated liposomes were multilayered and aggregates of AmB were embedded in the bilayers. These aggregates of AmB would be responsible for an intensive positive peak around 330 nm and reduced toxicity. Despite the decrease in toxicity, the activity of the precipitated liposomes against Candida albicans remained almost equipotent to that of the film-swollen liposomes. Therefore, liposomes prepared by the precipitation method are less toxic but equally as active.


Leukemia inhibitory factor modulates interleukin-1beta-induced activation of the hypothalamo-pituitary-adrenal axis.
We have shown that leukemia inhibitory factor (LIF) is expressed in corticotroph cells and stimulates POMC gene expression and ACTH secretion in vivo and in vitro. We therefore examined the regulation of in vitro and in vivo pituitary LIF expression by cytokines known to stimulate the hypothalamo-pituitary-adrenal axis. In the corticotroph cell line AtT-20/D16v-F2, recombinant murine interleukin-1beta (IL-1beta; 0.1-10.0 ng/ml) caused a 5- to 10-fold increase in LIF messenger RNA (mRNA) levels. LIF mRNA expression was induced as early as 1 h, peaked at 2 h, and still persistently elevated above the baseline after 8 h. This effect of IL-1beta on LIF mRNA expression was abolished by preincubation with human IL-1 receptor antagonist (100 ng/ml) or antimurine IL-1beta antibody (10 microg/ml). Tumor necrosis factor-alpha (20 ng/ml) only modestly increased LIF mRNA, but was synergistic with IL-1beta (up to 2.5-fold). In contrast, IL-2 and IL-6 did not alter LIF mRNA. In C57BL/6 mice, i.p. injection of 100 ng IL-1beta increased plasma ACTH and corticosterone levels after 1 h (P < 0.02). In addition, pituitary LIF mRNA content was increased for up to 2 h in response to IL-1beta. In comparison to wild-type (+/+) B6D2F1 mice, LIF knockout mice with a deleted LIF gene (-/-) exhibited decreased plasma ACTH (631 +/- 61 vs. 376 +/- 50 pg/ml; P < 0.01) and corticosterone (783 +/- 85 vs. 433 +/- 51 ng/ml; P < 0.01) levels 1 h after i.p. IL-1beta administration. In conclusion, corticotroph LIF mRNA expression is specifically stimulated by IL-1beta and tumor necrosis factor-alpha. The attenuated hypothalamo-pituitary-adrenal response to IL-1beta in LIF knockout mice indicates that the effect of IL-1beta on ACTH secretion is modulated by LIF. Thus, LIF appears to function as an immune-neuroendocrine modulator signaling the hypothalamo-pituitary-adrenal axis.


Serum fibrinogen-fibrin related antigen and protamine sulfate test in patients with septic abortion and acute renal failure.
Decreased platelet count and platelet adhesiveness as well as increased values of the protamine sulfate test were found in 26 patients with septic abortion (9 of them anuric). Serum fibrinogen-fibrin related antigen (FR-antigen) values, detected in 13 patients (7 of them anuric) were greatly increased although euglobulin lysis time was rather prolonged (more than 400 min). Less increased FR-antigen values were noted in 15 cirrhotic patients with enhanced fibrinolytic activity in the circulating blood (euglobulin lysis time less than 120 min). These findings suggest that an important increase of FR-antigen in serum is likely to indicate a local fibrinolytic response to an initial coagulation event. Since platelet count and adhesiveness as well as FR-antigen and protamine sulfate test were similarly changed in patients with septic abortion who developed acute renal failure and in those who did not, it seems that the above mentioned parameters are not predictive for the evolution of thrombotic deposits and for possible renal complications following an episode of disseminated intravascular coagulation.


Minimally invasive distraction technique for prone posterior ankle and subtalar arthroscopy.
Prone ankle and subtalar arthroscopy is challenging in part due to the limited working space in these joints. Fourteen patients undergoing prone posterior arthroscopy with a novel skeletal traction method were reviewed and the technique detailed. No complications were observed in 14 patients treated with a minimally invasive skeletal traction technique for prone ankle and subtalar arthroscopy and 38 patients treated with the same traction device during supine ankle arthroscopy. Minimally invasive skeletal traction can be used safely for prone posterior ankle and subtalar arthroscopy.


Acceleration of wound healing in aged rats by topical application of transforming growth factor-beta(1).
The impaired wound healing associated with aging may reflect inadequate secretion or delivery of cytokines. Transforming growth factor-beta(1) is a mitogenic polypeptide with beneficial effects on wound healing. In the present study we questioned whether topical administration of transforming growth factor-beta(1) could improve the wound healing process in aged rats in vivo. Wound repair (from 1 to 14 days) was analyzed in full-thickness incisional wounds from 2-year-old rats with or without a single topical application of transforming growth factor-beta(1) (1 microg/wound) at the time of wounding. Identical wounds from 3-month-old, untreated rats served as controls. Histologic analysis showed a marked delay in several aspects of wound repair in the aged rats in comparison with that noted in the younger animals. Immunostaining of the wounds for proliferating cell nuclear antigen showed a reduction in the number of cycling fibroblasts in old rats. In addition, the number of capillaries per unit area of the wound as determined by a stain for Griffonin (Bandeiraea) simplicifolia lectin, and the number of inflammatory cells as identified by an antibody specific for macrophages, were also reduced in the wound area in old rats. Treatment with transforming growth factor-beta(1) resulted in marked enhancement of the following parameters: cell proliferation, inflammatory cell and fibroblast influx, wound closure, and angiogenesis. As seen with in situ hybridization, a similar temporal pattern of expression of messenger RNAs corresponding to type I procollagen and Secreted Protein, Acidic and Rich in Cysteine (osteonectin), known to be prevalent in healing wounds, was observed in both young and aged rats. However, the levels of mRNA corresponding to these secreted proteins appeared to be reduced in wound tissue from aged rats. Treatment with transforming growth factor-beta(1) subsequently resulted in an increase in the expression of both type I procollagen and Secreted Protein, Acidic and Rich in Cysteine mRNA in the wound tissue from aged rats. In summary, a single topical application of transforming growth factor-beta(1) to the wounds of aged rats at the time of wounding was associated with a healing response that, in all the parameters of wound repair examined, was similar to that of young rats. Topical transforming growth factor-beta(1) might therefore be beneficial in the treatment of dermal wounds in the aged.


Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.
When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces.SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies.


Spontaneous resolution of retinal detachment occurring after macular hole surgery.
To document the spontaneous resolution of retinal detachment developing after macular hole surgery. We identified all patients who developed a postoperative retinal detachment after undergoing macular hole surgery at Washington University School of Medicine, St Louis, Mo; the surgery was performed by one of us (L.V.D.P. or H.J.K.) between 1991 and 1996. Six of 73 eyes developed a postoperative retinal detachment; the retinal detachment was inferior in all cases. Two eyes that had inferior retinal breaks underwent further surgery to repair the retinal detachment. Retinal breaks could not be identified in the other 4 eyes; the retinal detachment resolved without further surgery in all 4 of these eyes. The recognition that retinal detachment occurring after macular hole surgery can resolve without additional surgery may result in the avoidance of further surgical intervention in some eyes.


Jasmonic acid pathway is required in the resistance induced by Acremonium sclerotigenum in tomato against Pseudomonas syringae.
The use of fungal endophytes is considered as a new tool to confer resistance in plants against stresses. However, the mechanisms involved in colonization as well as in the induction of resistance by the endophytes are usually unclear. In this work, we tested whether a fungal endophyte isolated from an ancestor of wheat could induce resistance in plants of a different class from the ones that were isolated from the beginning. Seeds of Solanum lycopersicum were inoculated with Acremonium sclerotigenum and after four weeks, seedlings were inoculated with the bacterium Pseudomonas syringae pv tomato. Plants inoculated with endophytes showed significantly lower symptoms of infection as well as lower levels of colony forming units compared with control plants. Moreover, the presence of the endophytes induced an enhancement of Jasmonic acid (JA) upon inoculation with P. syringae compared with endophyte free plants. To ascertain the implication of JA in the resistance induced by A. sclerotigenum, two mutants defective in JA were tested. Results showed that the endophyte is not able to induce resistance in the mutant spr2, which is truncated in the first step of JA biosynthesis. On the contrary, acx1 mutant plants, which are unable to synthesize JA from OPC8, show a phenotype similar to wild type plants. Moreover, experiments with GFP-tagged endophytes showed no differences in the colonization in both mutants. In conclusion, the jasmonic acid pathway is required for the resistance mediated by the endophyte A. sclerotigenum in tomato against the biotrophic bacterium P. syringae but is not necessary for the colonization.


An examination of the effects of labor efficiency on the profitability of grass-based, seasonal-calving dairy farms.
The seasonality of grass-based, seasonal-calving dairy systems results in disproportionately higher labor demands during the spring, when cows are calving, than in the remaining seasons. This study aimed to (1) examine the relationship between labor efficiency and profitability; (2) investigate strategies to reduce the hours worked per day by the farmer, family, and farm staff in the spring by having certain tasks outsourced; and (3) quantify the economic implications of those strategies. Data from an existing labor efficiency study on Irish dairy farms were used in conjunction with economic performance data from the farms. Tasks that required the highest level of farm labor per day in the spring were identified and hypothetical strategies to reduce the farm hours worked per day were examined. A stochastic budgetary simulation model was then used to examine the economic implications of employing these strategies and the effects of their use in conjunction with a proportionate increase in cow numbers that would leave the hours worked per day unchanged. The strategies were to use contractors to perform calf rearing, machinery work, or milking. Contracting out milking resulted in the greatest reduction in hours worked per day (5.6 h/d) followed by calf rearing (2.7 h/d) and machinery work (2 h/d). Reducing the hours worked per day by removing those tasks had slight (i.e., <5%) negative effects on profitability; however, maintaining the farm hours worked per day while utilizing the same strategies and increasing herd sizes resulted in profitable options. The most profitable scenario was for farms to increase herd size while contracting out milking.


Spatiotemporal chaos in excised larynx vibrations.
Spatiotemporal chaos in excised larynx vibrations is reported using high-speed digital imaging. Spatiotemporal correlation and eigenmode analyses are applied to describe the spatiotemporal dynamics of the vocal fold vibrations and to investigate the effects of subglottal pressure. High subglottal pressures cause spatiotemporal chaos with decreased spatiotemporal correlation and increased entropy in the vocal fold vibrations. Spatiotemporal analysis shows a valuable biomedical application in investigating the spatiotemporal chaotic dynamics of the vocal fold system.


Probable clonal development of foreign-body-induced murine sarcomas.
The number of cells from which tumors induced by subcutaneous implantation of foreign bodies develop was studied in BALB/c mice with X-chromosome-inactivation mosaicism. Because only one of the two X-chromosomes is active in XX somatic cells, a female mouse heterozygous at the X-linked phosphoglycerate kinase (PGK) locus for Pgk-1b and Pgk-1a has two types of cells. In one population Pgk-1b is active and B-enzyme is produced, whereas in the other population Pgk-1a is active and A-type enzyme is synthesized. Normal tissues from these mosaic mice display both enzyme types, but a tumor that develops from a single cell exhibits only one of the two PGK enzyme types. Of 11 sarcomas induced by Millipore filters, 8 showed single-enzyme PGK phenotypes in primary tumors and in tissue cultures derived from them. The 3 other primary sarcomas showed double-enzyme phenotypes. However, transplantation of cultured cells from 2 of these sarcomas resulted in tumors with single-enzyme PGK phenotypes. Thus the data provide confirmatory evidence for the suggestion that most foreign-body-induced sarcomas develop clonally or from a relatively few cells.


Mixed connective tissue disease in childhood: a nationwide retrospective study in Japan.
Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a nationwide prospective study. The diagnostic significance of Raynaud's phenomenon and positive anti-RNP antibody was confirmed, and additional symptoms including swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels of myogenic enzymes, were variably positive. These clinical and laboratory characteristics of MCTD were critically different from those of systemic lupus erythematosus, indicating that MCTD is an independent entity of disease.


Increased joint loads during walking--a consequence of pain relief in knee osteoarthritis.
Joint pain is a primary symptom in knee osteoarthritis (OA), but the effect of pain and pain relief on the knee joint mechanics of walking is not clear. In this study, the effects of local knee joint analgesia on knee joint loads during walking were studied in a group of knee osteoarthritis patients. A group of healthy subjects was included as a reference group. The joint loads were calculated from standard gait analysis data obtained with standardised walking speed (4 km/h). The gait analyses were performed before and after pain relief by intra-articular injections of 10 mL lidocaine (1%). Pre-injection measurements revealed lower joint loads in the OA group compared to the reference group. Following injections pain during walking decreased significantly and the joint loads increased in the OA group during the late single support phase to a level comparable to the reference group. Although the patients walked with less compressive knee joint forces compared to the reference group, the effects of pain relief may accelerate the degenerative changes.


A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis.
The purpose of this study was to compare the therapeutic efficacy of a hydrocolloid dressing (Actiderm) over a medium strength corticosteroid (triamcinolone acetonide (TAA) 0.1% cream) with that of a highly potent corticosteroid (clobetasol propionate 0.05% cream) in palmo-plantar pustulosis and localized pustular psoriasis. It was a randomized, open, prospective, right-left comparative trial in 19 patients. The Actiderm dressing and the TAA cream were applied every third day, whereas the clobetasol cream was applied twice daily for 4 weeks. Both treatments resulted in a significant improvement. On completion of treatment, complete clearance was found in 13 patients (63%) with Actiderm plus TAA, but in only 3 patients (21%) with clobetasol (p = 0.001). Four weeks after stopping therapy, the clinical parameters had returned to their pre-treatment level, except for erythema on the Actiderm plus TAA treated lesions (p less than 0.05). No clinically important adverse effects were reported or observed; in particular there was no sign of skin atrophy at the end of study. The results of this study demonstrate that Actiderm applied over a medium strength corticosteroid every third day is highly effective against palmoplantar pustulosis and localized pustular psoriasis. However, it is necessary to develop treatment regimens to maintain the improvement achieved.


OpenWorm: an open-science approach to modeling Caenorhabditis elegans.
OpenWorm is an international collaboration with the aim of understanding how the behavior of Caenorhabditis elegans (C. elegans) emerges from its underlying physiological processes. The project has developed a modular simulation engine to create computational models of the worm. The modularity of the engine makes it possible to easily modify the model, incorporate new experimental data and test hypotheses. The modeling framework incorporates both biophysical neuronal simulations and a novel fluid-dynamics-based soft-tissue simulation for physical environment-body interactions. The project's open-science approach is aimed at overcoming the difficulties of integrative modeling within a traditional academic environment. In this article the rationale is presented for creating the OpenWorm collaboration, the tools and resources developed thus far are outlined and the unique challenges associated with the project are discussed.


The influence of age on the behaviour of carcinoma of the breast.
A consecutive series of 1530 patients with carcinoma of the breast has been reviewed to study the influence of age and marital status on the disease.The risk of developing breast cancer increases with age, though a peak may be reached at 75 years. The risk of developing a tumour of advanced clinical stage at presentation apparently increases with age. Local recurrence rates and mortality rates are similar at all ages. It is concluded that the therapy required is similar in all age groups.The increased risk of developing breast cancer in "never married" women is in the postmenopausal period. Survival rates and the distribution of the various presenting clinical stages are similar in both single and married patients.Though ageing and marital status have an initiating effect on breast cancer, they do not have a continuing effect on the established disease.


Fitts' Theorem and Movement Time Dissociation for Amplitude and Width Manipulations: Replying to Hoffmann.
The commentary by Errol Hoffmann asserts that previous work by our group provides the spurious conclusion that amplitude and width manipulations to a movement environment elicit dissociable relations between movement time (MT) and P. M. Fitts' (1954) index of difficulty (ID). Hoffmann concludes that any such dissociation is the result of actions evoked entirely as ballistic. In this reply, we demonstrate that Hoffmann's commentary is a clear misrepresentation of the study goals and conclusions stated by our group. Additionally, we provide kinematic evidence that actions involving online trajectory amendments are associated with dissociable MT-ID relations for amplitude versus width manipulations. Finally, we contend that the kinematic analyses of movement trajectories, and Hoffmann's failure to acknowledge its importance, is an important step in further understanding speed-accuracy relations in human movement.


The association between periodontal disease and obesity among adults in Jordan.
To determine the relationship between periodontitis and overweight/obesity among Jordanians. A systematic random sample of 340 persons aged between 18 and 70 years was selected from those who accompanied patients during their visit to the outpatient clinics in the medical centre of Jordan University of Science and Technology in north of Jordan. All participants underwent periodontal examination, had anthropometric measurements, and completed the questionnaire. Periodontitis was defined as presence of four or more teeth with one or more sites with probing pocket depth >or=4 mm and clinical attachment loss >or=3 mm. Only 14% of normal weight participants had periodontal disease whereas 29.6% of overweight and 51.9% of obese participants had periodontal disease. Periodontitis was more prevalent among subjects with high waist circumference (WC) and among subjects with high waist-to-hip ratio. After adjusting for important variables, only body mass index (BMI)-defined obesity [odds ratio (OR)=2.9, 95% confidence interval (CI): 1.3, 6.1], high WC (OR=2.1, 95%CI: 1.2, 3.7), and high fat per cent (OR=1.8, 95% CI: 1.03, 3.3) remained significantly associated with increased odds of periodontitis. BMI-defined obesity, high WC, and high fat per cent were significantly associated with increased odds of having periodontitis.


Decreased myocyte tension development and calcium responsiveness in rat right ventricular pressure overload.
The contractile dysfunction observed in end-stage myocardial hypertrophy has at its base an abnormality in myocyte function. However, whether depressed contractile function is related to an alteration in contractile protein function is presently unknown. Contractile force, tension, and calcium responsiveness were measured in single-skinned myocytes isolated from rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced by pulmonary artery constriction for 36 weeks and was associated with significant myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a force transducer and motor. Isometric force was measured over a wide range of calcium concentrations at two sarcomere lengths (SLs). Maximal force was increased in the RVH group: 1.20 +/- 0.10 versus 1.62 +/- 0.13 mg at SL = 2.0 microns and 1.33 +/- 0.10 versus 1.84 +/- 0.15 mg at SL = 2.3 microns (P < .05). Maximal tension, however, was reduced in the RVH group: 24.3 +/- 1.91 versus 37.5 +/- 2.92 mN/mm2 at SL = 2.0 microns and 27.4 +/- 1.78 versus 41.8 +/- 3.19 mN/mm2 at SL = 2.3 microns (P < .01). The concentration of calcium ions required for half-maximal activation was increased in the RVH group: 2.64 +/- 0.13 versus 3.47 +/- 0.22 mumol/L at SL = 2.0 microns and 2.23 +/- 0.15 versus 2.86 +/- 0.18 mumol/L at SL = 2.3 microns (P < .01). The slope of the force-calcium relationship (Hill coefficient) was decreased in the RVH group at SL = 2.0 microns (4.3 +/- 0.4 versus 3.1 +/- 0.2, P = .04) but not at SL = 2.3 microns (3.8 +/- 0.2 versus 3.6 +/- 0.2, P = NS). These results suggest that the depressed cardiac function of end-stage myocardial hypertrophy may be due, in part, to altered contractile protein function.


Identical twins with mature cystic teratomas treated with laparoscopic surgery: Two case reports.
Mature cystic teratomas are the most common among all ovarian neoplasms, representing 30-40% of the cases. However, to the best of our knowledge, there have been only two reports of mature cystic teratomas occurring in identical twins to date. We herein report a case of identical twins with mature cystic teratomas who were treated with laparoscopic surgery. A 32-year-old woman was referred to our hospital due to a tumor in the right ovary. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Two years later, the identical twin of the abovementioned patient was referred to our hospital also due to a right ovarian tumor. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Therefore, for early diagnosis, it may be important to consider the possibility of mature cystic teratoma in the identical twin of a patient, even in the absence of symptoms.


Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.
The presence of hepatitis B virus (HBV) covalently closed circular (ccc) DNA (cccDNA), which serves as a template for viral replication and integration of HBV DNA into the host cell genome, sustains liver pathogenesis and constitutes an intractable barrier to the eradication of chronic HBV infection. The current antiviral therapy for HBV infection, using nucleos(t)ide analogues (NAs), can suppress HBV replication but cannot eliminate integrated HBV DNA and episomal cccDNA. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a powerful genetic tool that can edit integrated HBV DNA and minichromosomal cccDNA for gene therapy, but its expression and delivery require a viral vector, which poses safety concerns for therapeutic applications in humans. In the present study, we used synthetic guide RNA (gRNA)/Cas9-ribonucleoprotein (RNP) as a nonviral formulation to develop a novel CRISPR/Cas9-mediated gene therapy for eradicating HBV infection. We designed a series of gRNAs targeting multiple specific HBV genes and tested their antiviral efficacy and cytotoxicity in different HBV cellular models. Transfection of stably HBV-infected human hepatoma cell line HepG2.2.15 with HBV-specific gRNA/Cas9 RNPs resulted in a substantial reduction in HBV transcripts. Specifically, gRNA5 and/or gRNA9 RNPs significantly reduced HBV cccDNA, total HBV DNA, pregenomic RNA, and HBV antigen (HBsAg, HBeAg) levels. T7 endonuclease 1 (T7E1) cleavage assay and DNA sequencing confirmed specific HBV gene cleavage and mutations at or around the gRNA target sites. Notably, this gene-editing system did not alter cellular viability or proliferation in the treated cells. Because of their rapid DNA cleavage capability, low off-target effects, low risk of insertional mutagenesis, and readiness for use in clinical application, these results suggest that synthetic gRNA/Cas9 RNP-based gene-editing can be utilized as a promising therapeutic drug for eradicating chronic HBV infection.


Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism.
Stress can exacerbate a number of psychiatric disorders, many of which are associated with prefrontal cortical (PFC) cognitive deficits. Biochemical studies demonstrate that mild stress preferentially increases dopamine turnover in the PFC. Our study examined the effects of acute, mild stress exposure on higher cognitive function in monkeys and the role of dopaminergic mechanisms in the stress response. The effects of loud (105-dB) noise stress were examined on a spatial working memory task (delayed response) dependent on the PFC, and on a reference memory task with similar motor and motivational demands (visual pattern discrimination) dependent on the inferior temporal cortex. The role of dopamine mechanisms was tested by challenging the stress response with agents that decrease dopamine receptor stimulation. Exposure to noise stress significantly impaired delayed-response performance. Stress did not impair performance on "0-second" delay control trials and did not alter visual pattern discrimination performance, which is consistent with impaired PFC cognitive function rather than nonspecific changes in performance. Stress-induced deficits in delayed-response performance were ameliorated by pretreatment with drugs that block dopamine receptors (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in rodents (clonidine, naloxone hydrochloride). These results indicate that stress impairs PFC cognitive function through a hyperdopaminergic mechanism. Stress may take the PFC "off-line" to allow more habitual responses mediated by posterior cortical and subcortical structures to regulate behavior. This mechanism may have survival value, but may often be maladaptive in human society, contributing to the vulnerability of the PFC in many neuropsychiatric disorders.


Evaluation of parameters in peptide mass fingerprinting for protein identification by MALDI-TOF mass spectrometry.
Protein identification by peptide mass fingerprinting, using the matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), plays a major role in large proteome projects. In order to develop a simple and reliable method for protein identification by MALDI-TOF MS, we compared and evaluated the major steps in peptide mass fingerprinting. We found that the removal of excess enzyme from the in-gel digestion usually gave a few more peptide peaks, which were important for the identification of some proteins. Internal calibration always gave better results. However, for a large number of samples, two step calibrations (i.e. database search with peptide mass from external calibration, then the use of peptide masses from the search result as internal calibrants) were useful and convenient. From the evaluation and combination of steps that were already developed by others, we established a single overall procedure for peptide identification from a polyacrylamide gel.


Priming memories of past wins induces risk seeking.
People are often risk averse when making decisions under uncertainty. When those decisions are based on past experience, people necessarily rely on their memories. Thus, what is remembered at the time of the choice should influence risky choice. We tested this hypothesis by priming memory for past outcomes in a simple risky-choice task. In the task, people repeatedly chose between a safe option and a risky option that paid off with a larger or smaller reward with a 50/50 chance. Some trials were preceded by a priming cue that was previously paired with one of the outcomes. We found that priming cues associated with wins caused people to become risk seeking, whereas priming cues associated with relative losses had little effect. These results suggest that people can be induced to be more risk seeking through subtle reminders of previous winning experiences.


Relationship between Hepatitis C Virus Infection and Iron Overload.
The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication". Articles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review. Iron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein. The growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.


Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic.
Little is known about the prevalence of specific depressive and anxiety disorders in women before a new course of assisted reproductive technology treatment. Few studies have adopted the proper psychiatric diagnostic procedures. All consecutive women visiting the assisted reproduction clinic of a university-affiliated medical centre, with the intention of starting a new assisted reproduction treatment course, were recruited. A psychiatrist made a diagnosis of psychiatric disorders using a structured interview, the Mini-International Neuropsychiatric Interview (MINI). Of a total of 112 participants, 40.2% had a psychiatric disorder. The most common diagnosis was generalized anxiety disorder (23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity did not differ from those without in terms of age, education, income, or years of infertility. Women with a history of previous assisted reproduction treatment did not differ from those without in depression or anxiety. Depressive and anxiety disorders were highly prevalent among women who visited an assisted reproduction clinic for a new course of the treatment. Demographic features and a history of previous assisted reproduction treatment were not risk factors for these psychiatric morbidities in the assisted reproduction clinic.


Developmental referrals of pre-school children in a diverse community in England: The importance of parental migration for referral rates.
Children born to migrant parents have higher rates of language difficulties, intellectual disability and autism. This study explores the relationship between migration, ethnicity and reasons for early years referrals to community paediatrics in a diverse multi-cultural population in a city in south west England. Observational retrospective study from a community paediatric service serving a multi-cultural urban population from June 2012 to February 2016. We tested associations of ethnicity and parental birth origin with reason for referral (developmental or non-developmental) for children under 5 years old and estimated crude rate ratios for referrals using population census data. Data were available for 514 children (52% white or mixed race, 16% Asian, 21% African diaspora, and 11.5% Somali); 53% had two UK-born parents while 22% had two migrant (non-UK-born) parents. Referrals were for developmental reasons in 307 (60%) including 86 for possible autism. Parental birth origin and ethnicity were associated with reason for referral (p < 0.001). Children from African diaspora, Asian or Somali backgrounds had more than twice the rate (rate ratio [RR] 2.37, 95% CI 1.88-2.99, p < 0.001) of developmental referrals compared with white or mixed-race children. Children of Somali or African diaspora ethnicity were, respectively, six-times (RR 5.99, 95% CI 3.24-10.8, p < 0.001) and four times (RR 4.23, 95% CI 2.44-7.29, p < 0.001) more likely to be referred for possible autism spectrum than their white or mixed-race peers. Developmental referral as a proportion of all referrals was twice as high among children with one migrant parent (20.4%) and three times as high among children with two migrant parents (29.5%), compared with children whose parents were both UK-born (10.7%). This study supports the importance of ethnicity and parental migration as factors in young children experiencing developmental difficulties, especially concerns about social communication or autism.


Occupational dermatitis artefacta: a clinical case in a flight attendant.
Dermatitis artefacta is a psychosomatic disorder characterized by cutaneous lesions that are self-inflicted by the patient, apparently due to itchy sensation. Usually, the patient denies any direct involvement with this condition and is rarely conscious of the underlying psychosomatic etiology. Authors report a case of a flight assistant with hypertrophic scars, symmetrically located on both upper arms. She referred chronic itchy sensation localized at the site where lesions were present; she referred relief only through continuous and forceful scratching. Considering the clinical history and after excluding other dermatological disorders, the diagnosis of dermatitis artefacta was made.


A rare cause of stridor: isolated tracheal amyloidosis.
A 50-year-old man presented to clinic with a two-year history of progressive exertional dyspnea and voice hoarseness. This history suggested upper airways obstruction, which was confirmed on computed tomography imaging that revealed extensive thickening of the proximal tracheal wall causing severe luminal narrowing. Bronchoscopic debulking was then performed and the samples obtained confirmed tracheal amyloidoisis. Extensive investigation confirmed that disease was localized solely to the trachea. Ultimately, after multiple discussions, the chosen treatment modality was radiotherapy, which proceeded relatively uneventfully and achieved excellent radiological and clinical response. Although tracheal amyloidosis is rare, it is most commonly observed as part of a multisystem presentation. The present report describes the even more uncommon diagnosis of isolated tracheal amyloidosis and highlights the role of radiotherapy in its management.


Ceftazidime: in vitro comparison with cephalothin, cefuroxime, and netilmicin. A Norwegian study.
The in vitro activity of ceftazidime has been compared with those of cephalothin, cefuroxime, and netilmicin against a variety of gram-positive and gram-negative bacteria in order to register sensitivity patterns in the western part of Norway. An agar dilution method was used for minimal inhibitory concentration (MIC) determination. Ceftazidime was the most active agent against Enterobacteriaceae; all isolates being inhibited by 2 mg/l or less, whereas netilmicin was slightly less active, especially against Providencia. Cephalothin and cefuroxime were markedly less active than the other two agents against Enterobacteriaceae. Ceftazidime and netilmicin were active against our Pseudomonas aeruginosa isolates (MICs less than or equal to 4 and less than or equal to 8 mg/l, respectively). Only netilmicin had useful activity against Acinetobacter calcoaceticus. Ceftazidime was the least active agent against Staphylococcus aureus; nearly all the isolates had MICs of 4-8 mg/l. Cefuroxime was the most active agent against Bacteroides fragilis, whereas ceftazidime was inactive. Ceftazidime may, in the future, be a useful alternative to the aminoglycosides in the treatment of serious gram-negative infections, particularly when P. aeruginosa might be involved.


Calciphylaxis after kidney transplantation: a rare but life-threatening disorder.
Calciphylaxis is a rare disorder characterized by vascular calcification and thrombosis of the subcutaneous microcirculation, leading to painful necrotic skin lesions and bearing a dreadfully high mortality rate. This syndrome is frequently also termed uraemic calcific arteriolopathy, since most cases are observed in patients with kidney failure. However, it is increasingly clear that calciphylaxis may also affect patients with normal or only slightly impaired renal function, including kidney transplant recipients. A precise definition of the characteristics and risk factors of calciphylaxis developing after kidney transplantation has been hindered by the extreme rarity of this condition, which also hampered the development of effective therapeutic strategies. In the present issue of CKJ, Guillén and colleagues report the largest case series of calciphylaxis in kidney transplant recipients to date, outlining several features that are apparently specific to this population. In this editorial, we briefly present the epidemiology and pathogenesis of calciphylaxis in different patient populations and discuss recent findings for its therapeutic management.


A method differentiating between bacterial adhesiveness and invasiveness in cell culture monolayer.
In order to differentiate between bacterial adhesiveness and invasiveness in cell culture monolayers, a method is reported which enables the same specimen to be examined by both scanning electron microscopy and Nomarski interference contrast microscopy. The source of error made by statistical variation when the two microscopical techniques are used individually is thus avoided.


Latex allergy in an orthognathic patient and implications for clinical management.
A 19-year-old girl with mild asthma had had 16 months of orthodontic treatment as part of the joint orthodontic/orthognathic approach to her 9.5 mm overjet. At the time of banding her second molars she developed latex protein allergy as a reaction to the operator's non-sterile powdered latex gloves. She also gave a history of allergy to other substances as well as of eczema. The patient was confirmed as allergic to latex protein by radioallergosorbent test (RAST) for IgE, requiring precautions be taken during further orthodontic procedures as well as during the subsequent orthognathic surgery for the underlying Class II skeletal pattern.


[Response to sertraline in adolescents with obsessive-compulsive disorder].
Previous studies have revealed that serotonin reuptake inhibitors are effective for the treatment of obsessive compulsive disorder (OCD) in children and adolescents. The clinical efficacy of sertraline (STL) for eight adolescents with OCD is examined. The patients are between 12 and 17 years old, being 3 of them female and 6 male. The severity is measured with OC-NIMH Scale and self-report Leyton-20 questionnaire. Administration of STL was begun at 50-200 mg/day, with maintenance dose of 50-150 mg/day. Seven patients responded adequately to STL for more than six months; a girl, aged 16, require discontinuation of STL because of untoward effects. The improvement starts before the 8th week of treatment. Six months later improvement scores with OC-NIMH and Leyton-20 rated near the 50%. In the seven patients with STL either have no untoward effects or mild effect. Favorable results are observed either in adolescents who received STL and cognitive therapy or those with STL as main treatment without any structure psychotherapy. After 6-21 months with STL, improvement has continue of has been increased.


[Quantitative analysis of 123I-BMIPP imaging in relation to exercise-redistribution 201Tl in patients with old myocardial infarction].
Myocardial kinetics of 123I-labeled 15-(p-iodophenyl)3R,S-methylpentadecanoic acid (BMIPP) was evaluated with BMIPP imaging in conjunction with stress-201Tl. We studied 20 patients with old myocardial infarction. BMIPP SPECT was obtained at 20 min and 3 h after injection. On a separate day, exercise stress-201Tl SPECT was performed at 10 min and 3 h after injection. Then, left ventricular myocardium was divided into 20 segments. For quantitative analysis, in each SPECT data, the maximum value (average counts per pixel) of all 20 myocardial segments was taken as 100%; the other values were calculated as a percentage of this maximum (Relative regional uptake, RRU). On the basis of stress-201Tl pattern, the myocardial segments were classified into 4 groups; normal 201Tl uptake, reversible 201Tl defect, fixed 201Tl defect and 201Tl defect with reverse redistribution. The 20 min BMIPP showed reduced activity compared with 3 h-201Tl (p < 0.001), especially in the area of 201Tl redistribution (50/111 segments, 45%), implicating impaired fatty acid utilization at resting condition. The washout rate of the segments with reversible 201Tl defect (-1.6 +/- 13.9%) was significantly lower than that of the segments with normal 201Tl uptake (9.0 +/- 9.8%) and fixed 201Tl defect (3.8 +/- 12.9%). Thus, BMIPP in combination with stress 201Tl imaging provides precise informations of impaired myocardial fatty acid utilization in patients with old myocardial infarction.


Fatty acid-amino acid conjugates are essential for systemic activation of salicylic acid-induced protein kinase and accumulation of jasmonic acid in Nicotiana attenuata.
Herbivory induces the activation of mitogen-activated protein kinases (MAPKs), the accumulation of jasmonates and defensive metabolites in damaged leaves and in distal undamaged leaves. Previous studies mainly focused on individual responses and a limited number of systemic leaves, and more research is needed for a better understanding of how different plant parts respond to herbivory. In the wild tobacco Nicotiana attenuata, FACs (fatty acid-amino acid conjugates) in Manduca sexta oral secretions (OS) are the major elicitors that induce herbivory-specific signaling but their role in systemic signaling is largely unknown. Here, we show that simulated herbivory (adding M. sexta OS to fresh wounds) dramatically increased SIPK (salicylic acid-induced protein kinase) activity and jasmonic acid (JA) levels in damaged leaves and in certain (but not all) undamaged systemic leaves, whereas wounding alone had no detectable systemic effects; importantly, FACs and wounding are both required for activating these systemic responses. In contrast to the activation of SIPK and elevation of JA in specific systemic leaves, increases in the activity of an important anti-herbivore defense, trypsin proteinase inhibitor (TPI), were observed in all systemic leaves after simulated herbivory, suggesting that systemic TPI induction does not require SIPK activation and JA increases. Leaf ablation experiments demonstrated that within 10 minutes after simulated herbivory, a signal (or signals) was produced and transported out of the treated leaves, and subsequently activated systemic responses. Our results reveal that N. attenuata specifically recognizes herbivore-derived FACs in damaged leaves and rapidly send out a long-distance signal to phylotactically connected leaves to activate MAPK and JA signaling, and we propose that FACs that penetrated into wounds rapidly induce the production of another long-distance signal(s) which travels to all systemic leaves and activates TPI defense.


Enhancing neurorehabilitation by targeting beneficial plasticity.
Neurorehabilitation is now one of the most exciting areas in neuroscience. Recognition that the central nervous system (CNS) remains plastic through life, new understanding of skilled behaviors (skills), and novel methods for engaging and guiding beneficial plasticity combine to provide unprecedented opportunities for restoring skills impaired by CNS injury or disease. The substrate of a skill is a distributed network of neurons and synapses that changes continually through life to ensure that skill performance remains satisfactory as new skills are acquired, and as growth, aging, and other life events occur. This substrate can extend from cortex to spinal cord. It has recently been given the name "heksor." In this new context, the primary goal of rehabilitation is to enable damaged heksors to repair themselves so that their skills are once again performed well. Skill-specific practice, the mainstay of standard therapy, often fails to optimally engage the many sites and kinds of plasticity available in the damaged CNS. New noninvasive technology-based interventions can target beneficial plasticity to critical sites in damaged heksors; these interventions may thereby enable much wider beneficial plasticity that enhances skill recovery. Targeted-plasticity interventions include operant conditioning of a spinal reflex or corticospinal motor evoked potential (MEP), paired-pulse facilitation of corticospinal connections, and brain-computer interface (BCI)-based training of electroencephalographic (EEG) sensorimotor rhythms. Initial studies in people with spinal cord injury, stroke, or multiple sclerosis show that these interventions can enhance skill recovery beyond that achieved by skill-specific practice alone. After treatment ends, the repaired heksors maintain the benefits.


Change Detection in Visual Short-Term Memory: The Relative Impact of Pairwise Switches and Identity Substitutions.
Numerous kinds of visual event challenge our ability to keep track of the objects that populate our visual environment from moment to moment. These include blinks, occlusion, shifting visual attention, and changes to object's visual and spatial properties over time. These visual events may lead to objects falling out of our visual awareness, but can also lead to unnoticed changes, such as undetected object replacements and positional exchanges. Current visual memory models do not predict which visual changes are likely to be the most difficult to detect. We examine the accuracy with which switches (where two objects exchange locations) and substitutions (where one or two objects are replaced) are detected. Inferior performance for one-object substitutions versus two-objects switches, along with superior performance for two-object substitutions versus two-object switches was found. Our results are interpreted in terms of object file theory, trade-offs between diffused and localized attention, and net visual change.


Haemostasis by Computerised Bipolar Diathermy.
Modern bipolar diathermy has certain limitations, especially regarding the regulation of the short coagulation course: it is somewhat awkward to use, is prone to mechanical malfunction and time consuming. The computerised bipolar diathermy system was originally developed for solving these problems in neurosurgery. It has now gained wide acceptance by all the surgical sub-specialities. Electronic feedback of the tissue impedance automatically starts and shuts off coagulation when a blood vessel is picked up by the forceps. The shut-off is related to a point in the impedance course that correlates to a temperature of 60 to 90°C, i.e. after coagulation has occurred and before complete desiccation, fulguration and sticking of the forceps has taken place.


Dynamics of caged ions in glassy ionic conductors.
At sufficiently high frequency and low temperature, the dielectric responses of glassy, crystalline, and molten ionic conductors all invariably exhibit nearly constant loss. This ubiquitous characteristic occurs in the short-time regime when the ions are still caged, indicating that it could be a determining factor of the mobility of the ions in conduction at longer times. An improved understanding of its origin should benefit the research of ion conducting materials for portable energy source as well as the resolution of the fundamental problem of the dynamics of ions. We perform molecular dynamics simulations of glassy lithium metasilicate (Li2SiO3) and find that the length scales of the caged Li+ ions motions are distributed according to a Levy distribution that has a long tail. These results suggest that the nearly constant loss originates from "dynamic anharmonicity" experienced by the moving but caged Li+ ions and provided by the surrounding matrix atoms executing correlated movements. The results pave the way for rigorous treatments of caged ion dynamics by nonlinear Hamiltonian dynamics.


Continuous depinning transition with an unusual hysteresis effect.
We identify a strange hysteresis which occurs in models of the depinning transition with both elastic and transient overshoot stresses. This hysteresis occurs generically despite the fact that the phase transition is still second order. We calculate the size of the hysteresis gap exactly in a large class of models. Because it is caused by irrelevant perturbations, the hysteresis does not show up in the field theory of the continuum limit. But since it is a real phenomenon it may be a cause for the hysteresis observed in natural depinning. We therefore discuss its experimental and numerical signatures which include microscopic nucleation.


Modification of auxinic phenoxyalkanoic acid herbicides by the acyl acid amido synthetase GH3.15 from Arabidopsis.
Herbicide-resistance traits are the most widely used agriculture biotechnology products. Yet, to maintain their effectiveness and to mitigate selection of herbicide-resistant weeds, the discovery of new resistance traits that use different chemical modes of action is essential. In plants, the Gretchen Hagen 3 (GH3) acyl acid amido synthetases catalyze the conjugation of amino acids to jasmonate and auxin phytohormones. This reaction chemistry has not been explored as a possible approach for herbicide modification and inactivation. Here, we examined a set of Arabidopsis GH3 proteins that use the auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) as substrates along with the corresponding auxinic phenoxyalkanoic acid herbicides 2,4-dichlorophenoxylacetic acid (2,4-D) and 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB). The IBA-specific AtGH3.15 protein displayed high catalytic activity with 2,4-DB, which was comparable to its activity with IBA. Screening of phenoxyalkanoic and phenylalkyl acids indicated that side-chain length of alkanoic and alkyl acids is a key feature of AtGH3.15's substrate preference. The X-ray crystal structure of the AtGH3.15·2,4-DB complex revealed how the herbicide binds in the active site. In root elongation assays, Arabidopsis AtGH3.15-knockout and -overexpression lines grown in the presence of 2,4-DB exhibited hypersensitivity and tolerance, respectively, indicating that the AtGH3.15-catalyzed modification inactivates 2,4-DB. These findings suggest a potential use for AtGH3.15, and perhaps other GH3 proteins, as herbicide-modifying enzymes that employ a mode of action different from those of currently available herbicide-resistance traits.


Effect of 10 pharmacologic probes on mRNA levels of inducible nitric oxide synthetase and selected inflammatory cytokines in a rat model of acute otitis media.
Ten drugs were screened for their ability to decrease inflammatory mediator (IL-6, inducible nitric oxide synthetase [iNOS], IL-1beta and monocyte chemotactic protein [MCP-1]) expression in a rat model of acute otitis media caused by Streptococcus pneumoniae. Six adult rats were randomly assigned to each of 12 groups corresponding to uninfected controls and treatments with saline, aminoguanidine, anisomycin, dexamethasone, ketorolac, L-N(G)-nitroarginine methylester, methylprednisolone, mycophenolic acid, pentoxiphylline, tacrolimus or WEB2086. Forty-eight h after the start of treatment, the ears of the animals in the 11 treatment groups were challenged with S. pneumoniae. Forty-eight h later, all animals were killed and middle ear mucosa was harvested and assayed for RNA message. Messages for IL-6, iNOS and MCP-1 were significantly increased as a result of infection. Most treatments decreased MCP-1 and four decreased IL-6 and iNOS. Tacrolimus and dexamethasone decreased IL-6, iNOS and MCP-1. These results show that pharmacological agents can modify the expression of inflammatory mediators in this model and may have clinically relevant effects.


Predictors of influenza vaccination in the U.S. among children 9-13years of age.
U.S. estimates of seasonal influenza (flu) vaccine uptake in 2014-2015 were 62% for 5-12year olds, dropping to 47% for 13-17year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9-13year old children. An online U.S. survey of mothers of children aged 9-13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status. There were 2363 respondents (Mean age=38years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p=n.s.). This sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.


Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation.
HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.


Olea europaea leaf (Ph.Eur.) extract as well as several of its isolated phenolics inhibit the gout-related enzyme xanthine oxidase.
In Mediterranean folk medicine Olea europaea L. leaf (Ph.Eur.) preparations are used as a common remedy for gout. In this in vitro study kinetic measurements were performed on both an 80% ethanolic (v/v) Olea europaea leaf dry extract (OLE) as well as on nine of its typical phenolic constituents in order to investigate its possible inhibitory effects on xanthine oxidase (XO), an enzyme well known to contribute significantly to this pathological process. Dixon and Lineweaver-Burk plot analysis were used to determine K(i) values and the inhibition mode for the isolated phenolics, which were analysed by RP-HPLC for standardisation of OLE. The standardised OLE as well as some of the tested phenolics significantly inhibited the activity of XO. Among these, the flavone aglycone apigenin exhibited by far the strongest effect on XO with a K(i) value of 0.52 μM. In comparison, the known synthetic XO inhibitor allopurinol, used as a reference standard, showed a K(i) of 7.3 μM. Although the phenolic secoiridoid oleuropein, the main ingredient of the extract (24.8%), had a considerable higher K(i) value of 53.0 μM, it still displayed a significant inhibition of XO. Furthermore, caffeic acid (K(i) of 11.5 μM; 1.89% of the extract), luteolin-7-O-β-D-glucoside (K(i) of 15.0 μM; 0.86%) and luteolin (K(i) of 2.9 μM; 0.086%) also contributed significantly to the XO inhibiting effect of OLE. For oleuropein, a competitive mode of inhibition was found, while all other active substances displayed a mixed mode of inhibition. Tyrosol, hydroxytyrosol, verbascoside, and apigenin-7-O-β-D-glucoside, which makes up for 0.3% of the extract, were inactive in all tested concentrations. Regarding the pharmacological in vitro effect of apigenin-7-O-β-D-glucoside, it has to be considered that it is transformed into the active apigenin aglycone in the mammalian body, thus also contributing substantially to the anti-gout activity of olive leaves. For the first time, this study provides a rational basis for the traditional use of olive leaves against gout in Mediterranean folk medicine.


Ankle joint load and leg muscle activity during lifting.
The load on the talocrural joint during three different ways of lifting was compared and discussed with biomechanical and ergonomical aspects. Healthy subjects lifted a 12.8-kg box from floor to table-level with bent and straight knees. The loading moment of force about the bilateral ankle axis was calculated by means of a computerized static sagittal plane model. Electromyography was recorded from the tibial anterior, gastrocnemius, and soleus muscles. The mean maximum loading moment was found to be 68 newton-meters with an estimated joint compressive force of 2.9 times body weight. The lowest loading moments obtained were associated with lifting the burden between bent knees and close to the pelvis.


An Improved Analytical Method for the Determination of Brown FK in Food using HPLC.
In this study, an improved analytical method for the detection of the colorant Brown FK in foods using high-performance liquid chromatography was developed. The method, which employed an RC-C18 column and diode array detection at 254 nm with sodium acetate solution and methanol as mobile phases, exhibited good linearity (R2 = 1.0), and its limits of detection and quantification were determined to be 0.06 and 0.19 μg/mL, respectively. The precision was found to be 0-1.2% and the accuracy was between 86.5% and 94.8%. Liquid chromatography-tandem mass spectrometry was also performed to identify Brown FK in peaks. The pretreatment method was optimized for three different food sample groups, i.e., seafood, noodles and other, affording recoveries of 86.5-92.8%, 90.8-94.8% and 90.0-92.3%, respectively. In addition, inter-laboratory testing was also conducted to check the precision.


Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans.
DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC-MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1-26-month-old rats and 111 in human heart and brain by 'stepped MRM' LC-MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.


The importance of using medical devices correctly.
Nurses should ensure medical devices are being used for their intended purpose. Nurses should check when equipment was last serviced and whether it has been adequately cleaned. The MDA should be informed of any adverse incidents or minor faults. Organisations also have a role to play in minimising adverse incidents.


Depressive disorder may be associated with raphe nuclei lesions in patients with brainstem infarction.
Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Åsberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei-damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. We did not assess the damage to the ascending projection fibers from the raphe nuclei. Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.


Characterization of peripheral blood inflammatory indicators and OCT imaging biological markers in diabetic retinopathy with or without nephropathy.
To observe the distribution characteristics of peripheral blood inflammatory indexes and retinal macular area optical coherence tomography (OCT) imaging biomarkers in patients with diabetic retinopathy (DR) with or without diabetic nephropathy (DN), in order to seek clinical biomarkers that can predict the development of DR and DN. A total of 169 inpatients with DR who visited the ophthalmology department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from October 2020 to June 2022 and had complete clinical data were collected, and the patients with DR were divided into two major groups, DR and DR/DN, according to whether they had DN, and then further divided into four subgroups, Non-proliferative DR(NPDR), proliferative DR(PDR), NPDR/DN and PDR/DN, according to the stage of DR. The distribution characteristics of peripheral blood inflammatory indexes [Neutrophil to lymphocyte ratio(NLR) and Platelet to neutrophil ratio(PLR)], renal function indexes [Cystatin-C(CYS-C), Creatinine(Crea), Uric acid(UA)and Urinary albumin to creatinine ratio(UACR)] and OCT imaging indexes [Hyperreflective foci(HRF), Disorgnization of retinal inner layers(DRIL), Outer retinal tubulations(ORTs), Central retinal thickness(CRT), Retinal nerve fiber layer(RNFL) and Ganglion cell layer(GCL)] were analyzed between the above subgroups. There was no difference between DR and DR/DN groups in terms of gender, family history of diabetes, duration of diabetes and Body mass index(BMI) (P>0.05), the mean age of the DR/DN group was significantly lower than that of the DR group (P<0.05), and the proportion of the DR/DN group with a history of hypertension was significantly higher than that of the DR group (P<0.05); there was no significant difference in hemoglobin A1C(HbA1c) between DR and DR/DN groups (P>0.05). (P>0.05), Hemoglobin(HGB) was significantly higher in the DR group than in the DR/DN group (P <0.05), NLR, PLR, Crea, UA and CYS-C were significantly higher in the DR/DN group than in the DR group (P<0.05); there was no significant difference in the comparison of HRF, DRIL, ORTs positive rate and CRT between the DR and DR/DN groups (P>0.05). RNFL and GCL thickness were significantly lower in the DR/DN group than in the DR group (P<0.05); history of hypertension (OR=2.759), NLR (OR=1.316), PLR (OR=1.009), Crea (OR=1.018), UA (OR=1.004), CYS-C (OR=3.742) were the independent (OR=0.951), age (OR=0.951), HGB (OR=0.976), RNFL (OR=0.909) and GCL (OR=0.945) were independent protective factors for DR/DN; RNFL (OR=0.899) and GCL (OR=0.935) were independent protective factors for NPDR/DN, RNFL (OR=0.852) and GCL (OR=0.928) were independent protective factors for PDR/DN. ROC curve analysis showed that the area under the curve (AUC) for CYS-C, PLR, Crea, UA and the combination of the four indicators to predict DR/DN were 0.717, 0.625, 0.647, 0.616 and 0.717, respectively. (1) Low age combined with hypertension HGB, NLR, PLR, CYS-C, Crea and UA may be serum biological markers for predicting DN in DR; meanwhile, PLR, CYS-C, Crea, UA and the combination of the four indicators can be used for risk assessment and adjunctive diagnosis of DN in DR combined with hypertension. (2) The RNFL and GCL thickness in the temporal aspect of the central macular sulcus may be imaging biological markers for predicting DN in DR; meanwhile, GCL thickness may have important value for risk prediction and diagnosis of DN in combination with DR.


Minimally Conjoined Omphalopagus Twins with a Body Stalk Anomaly.
Introduction This report will discuss a case of minimally conjoined omphalopagus twins (MCOTs) with a body stalk anomaly (BSA). Case Report We experienced monochorionic diamniotic (MD) twins born at 31 weeks. One infant was suspicious of BSA before birth, and another infant was normal. But normal infant had anal atresia with small intestine which was inserted behind the umbilicus. Twins had very short common umbilicus and infant with BSA had intestinal conjunction, two appendixes at the site of the colon, and a blind-ending colon. We diagnosed MCOTs. Discussion On the basis of the Spencer hypothesis, the etiology of MCOTs was that MD twins shared a yolk sac. However, this could not explain the presence of a BSA. It is necessary to consider the possible reasons for a singleton BSA. In addition, intestinal fusion occurred unequally in this case, although two appendixes were found in the same place, which might have occurred because of the balanced fusion.


Consecutive cyclic esotropia.
A 12-year-old girl who developed a cyclic esotropia following strabismus surgery for intermittent exotropia at the age of eight years is presented. Unusual findings and surgical results are described. We suggest the term of "consecutive cyclic esotropia" for this clinical entity.


Enantioselective C-H carbene insertions with homogeneous and immobilized copper complexes.
The efficiency of chiral bis(oxazoline)- and azabis(oxazoline)-copper complexes in the enantioselective carbene insertion into C-H bonds of cyclic ethers in homogeneous phase strongly depends on the structure of the substrate. The immobilization on laponite clay by electrostatic interactions not only allows the recovery and reuse of the heterogeneous catalysts, but in some cases also improves enantioselectivity and overall chemoselectivity, making possible reactions that do not take place or lead to low yields in solution, even with the commonly used Rh(2)[S-DOSP](4) catalyst.


Knowledge mapping of global trends for myasthenia gravis development: A bibliometrics analysis.
Myasthenia gravis (MG) is an autoimmune disease with acquired neuromuscular junction transmission disorders. In the last two decades, various pathogenesis, application of immunosuppressive agents, and targeted immunotherapy have been significant events. However, extracting the most critical information from complex events is very difficult to guide clinical work. Therefore, we used bibliometrics to summarize and look forward. Science Citation Index Expanded (SCI-E) from the Web of Science Core Collection (WoSCC) database was identified as a source of material for obtaining MG-related articles. Scimago Graphica, CiteSpace, VOSviewer, and bibliometrix were utilized for bibliometric analysis. Knowledge network graphs were constructed and visualized; countries, institutions, authors, journals, references, and keywords were evaluated. In addition, GraphPad Prism and Microsoft Excel 365 were applied for statistical analysis. As of October 25, 2022, 9,970 original MG-related articles were used for the bibliometric analysis; the cumulative number of citations to these articles was 236,987, with an H-index of 201. The United States ranked first in terms of the number of publications (2,877) and H-index (134). Oxford has the highest H-index (67), and Udice French Research University has the highest number of publications (319). The author with the highest average number of citations (66.19), publications (151), and H-index (53) was Vincent A. 28 articles have remained in an explosive period of citations. The final screening yielded predictive keywords related to clinical trials and COVID-19. We conducted a bibliometric analysis of 9,970 original MG-related articles published between 1966 and 2022. Ultimately, we found that future MG research hotspots include two major parts: (1) studies directly related to MG disease itself: clinical trials of various targeted biological agents; the relationship between biomarkers and therapeutic decisions, pathogenesis and outcome events, ultimately serving individualized management or precision therapy; (2) studies related to MG and COVID-19: different variants of COVID-19 (e.g., Omicron) on MG adverse outcome events; assessment of the safety of different COVID-19 vaccines for different subtypes of MG.


Prevalence of genital psoriasis in patients with psoriasis.
Psoriatic lesions in the genital area (GenPs) can cause considerable physical and emotional distress. To increase physician awareness, we estimated the GenPs prevalence among patients with psoriasis. An English language literature search was performed. Articles reporting GenPs prevalence met the search criteria and were included. Because GenPs is rarely reported in demographics of prospective clinical trials, GenPs prevalence and baseline demographics of patients with and without GenPs in two prospective randomized phase 3b trials (NCT02561806 and NCT02634801) involving patients with moderate-to-severe psoriasis are reported. Overall, 600 references were screened. Eighteen articles met the search criteria. Patient populations were highly heterogeneous across articles. Broadly, the presence of GenPs was either physician-reported (physical examinations) or patient-reported (questionnaires). In the literature, GenPs prevalence at the time of reporting ranged from 7% to 42% and the prevalence of GenPs at any time during the course of psoriasis ranged from 33% to 63%. In the two prospective clinical trials, the prevalence of GenPs at the time of enrollment was 35-42%. A substantial proportion of patients experience genital lesions at some time during the course of psoriasis. Increased awareness of GenPs prevalence may drive improved assessment and treatment.


Psychoneurotic disturbance and drug-taking in Borstal boys.
Their own accounts of their use of drugs, together with a detailed description of psychiatric history and present mental state, were obtained from a sample of institutionalized delinquents, Subjects reporting extensive involvement in drug abuse were found to be disturbed on a number of psychiatric variables; however, those reporting some limited abuse were less disturbed than subjects reporting no experience of drug taking. The results and their implications are discussed.


Microscopical localization on adenylate cyclase: a historical review of methodologies.
The histochemistry technique for localizing adenylate cyclase has been developed over the past two decades. Early efforts were directed at overcoming the criticism of the lead capture technique, the inhibition of the enzyme by fixation, and problems associated with the substrate. The introduction of alternative metal ions, strontium and cerium, offered solutions to the criticism of the lead capture technique. The inhibition of the enzyme by the various fixation methods used has been rarely overcome satisfactorily and the use of non-fixed material during incubation is one of the alternatives that has been suggested. The introduction of adenylate (beta-gamma-methylene) diphosphate as an alternative substrate offers a solution to the problems associated with commercially available adenylyl imidodiphosphate. Although no standard medium or method has been accepted by all researchers, the histochemical technique still has a place in the arsenal of the modern cell biologist. The technique localizes the active enzyme, as opposed to the protein, active and nonactive, by immunocytochemistry and the precursors of the protein by in situ hybridization methods.


Sediment sound speed inversion with time-frequency analysis and modal arrival time probability density functions.
The dispersion pattern of a received signal is critical for understanding physical properties of the propagation medium. The objective of this work is to estimate accurately sediment sound speed using modal arrival times obtained from dispersion curves extracted via time-frequency analysis of acoustic signals. A particle filter is used that estimates probability density functions of modal frequencies arriving at specific times. Employing this information, probability density functions of arrival times for modal frequencies are constructed. Samples of arrival time differences are then obtained and are propagated backwards through an inverse acoustic model. As a result, probability density functions of sediment sound speed are estimated. Maximum a posteriori estimates indicate that inversion is successful. It is also demonstrated that multiple frequency processing offers an advantage over inversion at a single frequency, producing results with reduced variance.


Thin-film electroencephalographic electrodes using multi-walled carbon nanotubes are effective for neurosurgery.
Intraoperative morphological and functional monitoring is essential for safe neurosurgery. Functional monitoring is based on electroencephalography (EEG), which uses silver electrodes. However, these electrodes generate metal artifacts as silver blocks X-rays, creating white radial lines on computed tomography (CT) images during surgery. Thick electrodes interfere with surgical procedures. Thus, thinner and lighter electrodes are ideal for intraoperative use. The authors developed thin brain electrodes using carbon nanotubes that were formed into thin sheets and connected to electrical wires. The nanotube sheets were soft and fitted the curve of the head very well. When attached to the head using paste, the impedance of the newly developed electrodes was 5 kΩ or lower, which was similar to that of conventional metal electrodes. These electrodes can be used in combination with intraoperative CT, magnetic resonance imaging (MRI), or cerebral angiography. Somatosensory-evoked potentials, auditory brainstem responses, and visually evoked potentials were clearly identified in ten volunteers. The electrodes, without any artifacts that distort images, did not interfere with X-rays, CT, or MR images. They also did not cause skin damage. Carbon nanotube electrodes may be ideal for neurosurgery.