What is the role of prosthesis insertion in esophageal carcinoma?
We review our experience with 13 patients in whom esophageal dilation was used for palliation of malignant esophageal obstruction and with five patients treated with esophageal prostheses for malignant esophagorespiratory fistula. Twelve of the 13 patients with dilation alone received satisfactory palliation and were able to eat a soft or regular diet. Four of five patients with esophagorespiratory fistulas had esophageal dilation followed by insertion of a esophageal prosthesis and received good palliation. Endoscopic insertion of esophageal prosthetic devices has become increasingly popular as a palliative procedure, despite lack of controlled trials either proving efficacy of this therapy or comparing it to radiation therapy with or without dilation of the esophagus. The reported mortality and morbidity rates for esophageal prosthesis insertion are higher than those reported for radiotherapy. There is little to suggest that prostheses are better than or even equal to radiotherapy alone or radiotherapy and bougienage. We review the reported series (greater than 2300 cases) of push-through prostheses insertions in esophageal cancer and compare prosthesis insertion to other therapy. The need for a carefully controlled trial of the different forms of therapy is emphasized, and guidelines for such a study are suggested.


Validity and Reliability Evidence of the Munro Scale for Perioperative Patients Part I: Correlation, Multiple Regression, and Reliability.
Background and Purpose: Patients undergoing surgery are at risk of pressure injury development and should be assessed to ensure measures are taken for prevention. The study's purpose was to examine the causal relationships and reliability of the Munro Pressure Injury Risk Assessment Scale for Perioperative Patients (Munro Scale). The Munro Scale is the first dynamic risk scale available for this patient population in the acute clinical setting. Methods: This study was a retrospective review to explore the relationships of the variables in the Munro Scale, identify the strongest predictors, and measure the reliability of previously collected data from two northeastern community hospitals. A total of 630 risk assessments were analyzed to obtain regression, correlation, and reliability evidence for the Munro Scale. Results: The correlation analysis among the 15 risk variables and combined comorbidities revealed commonalities among the variables and significant relationships to the final postoperative injury score. The model as a whole is significant to predict the final level of risk. Cronbach's α revealed a lower than anticipated reliability when compared to the Chinese, Turkish, and Brazilian versions of the Munro Scale. Conclusions: There are significant relationships among the variables, and the scale is acceptable for use in the acute perioperative practice setting. This study has both clinical and statistical significance.


Lipocalin-2 is dispensable in inflammation-induced sickness and depression-like behavior.
While the relationship between inflammation and depression is well-established, the molecular mechanisms mediating this relationship remain unclear. RNA sequencing analysis comparing brains of vehicle- and lipopolysaccharide-treated mice revealed LCN2 among the most dysregulated genes. As LCN2 is known to be an important regulator of the immune response to bacterial infection, we investigated its role in the behavioral response to lipopolysaccharide. To explore the role of LCN2 in modulating behavior following lipopolysaccharide administration using wild type (WT) and lcn2-/- mice. Using a within-subjects design, mice were treated with 0.33 mg/kg liposaccharide (LPS) and vehicle. Primary outcome measures included body weight, food consumption, voluntary wheel running, sucrose preference, and the tail suspension test. To evaluate the inflammatory response, 1 week later, mice were re-administered either vehicle or LPS and terminated at 6 h. While lcn2-/- mice had increased baseline food consumption and body weight, they showed a pattern of reduced food consumption and weight loss similar to WT mice in response to LPS. WT and lcn2-/- mice both recovered voluntary activity on the fourth day following LPS. LPS induced equivalent reductions in sucrose preference and TST immobility in the WT and lcn2-/- mice. Finally, there were no significant effects of genotype on inflammatory markers. Our data demonstrate that lcn2 is dispensable for sterile inflammation-induced sickness and depression-like behavior. Specifically, lcn2-/- mice displayed sickness and immobility in the tail suspension test comparable to that of WT mice both in terms of intensity and duration.


Nonprescription Products of Internet Retailers for the Prevention and Management of Herpes Zoster and Postherpetic Neuralgia: Analysis of Consumer Reviews on Amazon.
Herpes zoster affects approximately 1 million people annually in the United States, with postherpetic neuralgia as the most common complication. The frequent prescription of opioids as the first-line medication for herpes zoster or postherpetic neuralgia contributes to the increasing health care costs of their treatment. Despite the advent of internet retailers providing alternative products for the prevention and management these conditions, there are limited studies on the availability, ingredients, and consumer preference for the products. This study used the internet retailer Amazon to determine the availability of products for the management of herpes zoster and postherpetic neuralgia, and assessed consumer preference based on listed ingredients. The internet retailer Amazon was used to perform a search for products related to "shingles" in September 2020. Top products sorted by reviews and ratings were determined to be either shingles-specific (including "shingles" in either the product title or description) or shingles-nonspecific. Analysis of price, rating, type of vehicle, and ingredients was performed. The types of vehicles, ingredients, and percentages of positive and negative reviews related to "shingles" of the product groups were analyzed with a two-tailed two-sample proportions Z-test to assess the difference between shingles-specific and shingles-nonspecific products. Statistical significance was judged at P<.05. The top 131 products among over 3000 products retrieved were determined based on a rating of 4 or more stars after searching for the term "shingles" on Amazon. Forty-six of the 131 products (35.1%) were shingles-specific. Shingles-nonspecific products were more likely to have positive reviews mentioning "shingles" (P=.005). Vehicles, balms (P=.02), and salves (P=.04) were more likely to be shingles-specific, whereas tablets or capsules (P=.002) were more likely to be shingles-nonspecific. Among the ingredients analyzed, aloe vera was the top-ranked ingredient, included in 29 of the 131 total products (22.1%). Aloe vera (P=.01), lemon balm (P<.001), vitamin E (P=.03), and peppermint oil (P=.008) were more likely to be included in the shingles-specific products, whereas magnesium (P=.01) was more likely to be included in shingles-nonspecific products. There is an abundance of products and ingredients being used for the management and treatment of shingles with certain ingredients preferred by consumers. There is a discrepancy between approved ingredients and the ingredients preferred by consumers. Furthermore, there are insufficient studies on ingredients used by consumers on internet retailers such as Amazon, and future studies can focus on the effectiveness of popular ingredients to decrease misinformation on the internet.


NH4+-N versus pH and ORP versus NO3--N sensors during online monitoring of an intermittently aerated and fed membrane bioreactor.
Online sensors, which monitor the ammonia oxidation and the dissimilatory nitrate reduction process, can optimize aerobic and anoxic phase duration. The purpose of this study was to comparatively evaluate the effectiveness of online sensors that were in situ-located in an intermittently aerated and fed membrane bioreactor (IAF-MBR) system. Ammonium and nitrate nitrogen sensors equipped with ion-selective electrodes as well as pH and oxidation-reduction potential (ORP) sensors were employed to online monitoring and optimizing of ammonia oxidation and nitrate reduction processes. The "ammonia valley" or pH bending point, which is indicative of ammonia depletion, was effectively and repeatedly detected by measuring the pH profile, while the "nitrate knee" point, which indicates the completion of the denitrification process, was online-detected by obtaining the ORP profile. The "ammonia valley" and "nitrate knee" were detected at pH and ORP values of 6.47 ± 0.02 and - 162 ± 39 mV, respectively. The ORP and pH first derivatives (dORP/dt and dpH/dt) were found to be more suitable than the untransformed ORP and pH values in detecting pH and ORP inflection points and controlling the shift from the anoxic to the aeration phase. Specifically, the ORP and pH bending points were detected at dORP/dt and dpH/dt values of 1.64 ± 0.82 mV min-1 and 0.005 ± 0.001 min-1, respectively. Moreover, the ORP first derivative has appeared earlier than the ORP bending point.


Does somatization influence quality of life among older primary care patients?
Among older people, somatization has been reported to be common and to be predictive of high attendance in primary care. Its relationship with quality of life among older people has not been investigated. The objective was to establish whether, among older primary care attenders, somatized symptoms are independently associated with relevant measures of quality of life. Older primary care attenders (n = 127) completed measures of somatized symptoms, psychiatric status, physical health and health-related quality of life. Logistic regression analyses established independent relationships of health and sociodemographic variables with reports of overall quality of life, overall health, restriction of physical activities by health and restriction of social activities by health. For all four outcomes, somatized symptoms independently predicted poorer quality of life ratings. Somatized symptoms independently influence quality of life in older primary care patients and are worthy of clinical attention.


Synthesis of a Coumarin-Based Analogue of Schweinfurthin F.
The natural schweinfurthins are stilbenes with significant antiproliferative activity and an uncertain mechanism of action. To obtain a fluorescent analogue with minimal deviation from the natural structure, a coumarin ring system was annulated to the D-ring, creating a new analogue of schweinfurthin F. This stilbene was prepared through a convergent synthesis, with a Horner-Wadsworth-Emmons condensation employed to form the central stilbene olefin. After preparation of a tricyclic phosphonate via a recent and more efficient modification of the classic Arbuzov reaction, condensation was attempted with an appropriately substituted bicyclic aldehyde but the coumarin system did not survive the reaction conditions. When olefin formation preceded generation of the coumarin, the stilbene formation proceeded smoothly and ultimately allowed access to the targeted coumarin-based schweinfurthin analogue. This analogue displayed the desired fluorescence properties along with significant biological activity in the National Cancer Institute's 60-cell line bioassay, and the pattern of this biological activity mirrored that of the natural product schweinfurthin F. This approach gives facile access to new fluorescent analogues of the natural schweinfurthins and should be applicable to other natural stilbenes as well.


Survey of ecological environmental conditions and influential factors for public parks in Shanghai.
Urban public parks provide a recreational environment for residents, hence more and more citizens would spend time in parks, especially elderly and kids. Therefore, it is important to evaluate the quality of ecological environment inside parks. Therefore, this study conducted the first measurements in ten public parks of Shanghai to investigate heavy metals in air, soil and leaf, growth parameters of leaf, and ambient PM2.5 and black carbon (BC) concentrations. Results showed Al and Mg appeared the highest in air. Cr, Cu, Mn and Zn were dominating in soil. Ca and Mg were much greater in leaves. It was concluded geographical locations were major reasons to explain the level of heavy metals, which mainly came from vehicle emissions. A small portion was attributing to chemical industries nearby. PM2.5 concentrations ranged from 0.01 mg/m3 to 0.10 mg/m3, which met up level I and level II of air quality standard in China. BC concentrations ranged from 1000 ng/m3 to 6000 ng/m3. Via comparing the correlation between photosynthesis and PM2.5, as well as chlorophyll content and PM2.5, it was concluded that chlorophyll can be regarded as an indicator for assessing air quality, but not photosynthesis. Unexpectedly, a positive correlation was observed between the stomatal conductance and PM2.5 as well as BC, which might be attributed to plants resisting the ambient stress. The results of this study can be used for assessments of air quality and health exposure inside parks, and also could provide urban policy maker with scientific evidences for urban park planning.


Orthotic and prosthetic prescriptions for today and tomorrow.
The prosthetic and orthotic field is in constant flux, with newer technology and materials being incorporated into everyday practice. Research into the field is increasing as interest in restoring or simulating lost human function becomes more of a reality with advances in computer and microprocessor technology. This article explores the world of braces and artificial limbs, and reviews the inherent challenges encountered during rehabilitation of patients who have these specific orthotic/prosthetic needs. The authors provide quick-reference tables and highlight critical information needed to manage patients. It examines newer technology being developed and gauges how close the field really is to the era of Steve Austin, television's Six-Million Dollar Man.


Studies on the control of myelinogenesis. IV. Neuronal induction of Schwann cell myelin-specific protein synthesis during nerve fiber regeneration.
The temporal sequence of axon-Schwann cell interaction during regeneration is examined in cat tibial nerves surgically denervated for 8 weeks and, subsequently, coated to a freshly severed peroneal nerve for 3 weeks. Prior to association with regenerating axons, Schwann cells resident in denervated and reinnervated stumps failed to synthesize proteins co-migrant with P0, P1, and P2 myelin proteins in contrast to normal nerves. Axonal association with Schwann cells stimulated synthesis of amino acid-labeled proteins co-migrating with myelin-specific proteins prior to elaboration of myelin lamellae. Radioactivity from these peaks was precipitated by antibodies raised against myelin-specific proteins. The synthesis of P1 and P2 proteins was evident before P0 synthesis in reinnervated stumps. Immunocytochemical staining with antibody to P0, P1, P2, and myelin-associated glycoprotein (MAG) appeared only after myelin lamellae had been formed. These data suggest that Schwann cells: (a) synthesize proteins co-migrant with P1, P2, P0, and MAG in normal cat nerves; (b) cease detectable manufacture of these proteins after axonal loss; (c) regain their capacity to synthesize these proteins upon re-establishment of axonal association; and (d) during regeneration, express the synthesis of P1 and P2 before that of P0.


Macular circulation and the flying corpuscles phenomenon.
The entoptic phenomenon of the flying corpuscles (FLC) consists of the perception of one's own leukocytes flowing in the perifoveal capillaries. A method has been developed to investigate the type of motion of the FLC, their relative number and speed, and their distribution over the central visual field. The results in 38 patients with disease affecting the macula correlated well with the clinical findings obtained by ophthalmoscopy, visual field tests, and fluorescein angiography. The test is noninvasive, inexpensive, easy to perform, and provides information on the perifoveal retinal circulation and on macular function.


[Anassociation study between OPHN1 gene rs492933 polymorphism and mental retardation in children of the Qinba Mountain region.].
The OPHN1 gene encodes a Rho-GTPase activating protein (RhoGAP), and mutations in OPHN1 are responsible for non-specific X-linked mental retardation (NSMR). A SNP located in the 5'-untranslated region (UTRs) of OPHN1 (rs492933) was examined by PCR-RFLP to assess its contribution to cognitive ability in 234 unrelated healthy and MR children in the Qinba Mountain region in Shaanxi. The allelic frequencies of rs492933 were 0.826 for the C allele and 0.174 for the T allele. Genotype frequencies and allelic frequencies were not significantly different between the MR and the controls, or between the borderline group and the controls. In conclusion, there is no association between the OPHN1 gene polymorphism and NSMR in the Qinba Mountain region children.


Distant plant homologues: don't throw out the baby.
Plants and metazoans share many similarities in terms of conserved proteins. Antibodies have been used extensively to detect remote homologues, many of which are yet to be identified conclusively. Genome sequencing and the creation of novel sequence or structure comparison programs have assisted greatly in the identification of distant protein homologues. The continuing development of new software algorithms and the combining of bioinformatics with proteomics offer hope that remaining homologues will be soon identified.


Mapping the functional domains of human transcobalamin using monoclonal antibodies.
Recombinant human transcobalamin (TC) was probed with 17 monoclonal antibodies (mAbs), using surface plasmon resonance measurements. These experiments identified five distinct epitope clusters on the surface of holo-TC. Western blot analysis of the CNBr cleavage fragments of TC allowed us to distribute the epitopes between two regions, which spanned either the second quarter of the TC sequence GQLA...TAAM(103-198) or the C-terminal peptide LEPA...LVSW(316-427). Proteolytic fragments of TC and the synthetic peptides were used to further specify the epitope map and define the functional domains of TC. Only one antibody showed some interference with cobalamin (Cbl) binding to TC, and the corresponding epitope was situated at the C-terminal stretch TQAS...QLLR(372-399). We explored the receptor-blocking effect of several mAbs and heparin to identify TC domains essential for the interaction between holo-TC and the receptor. The receptor-related epitopes were located within the TC sequence GQLA...HHSV(103-159). The putative heparin-binding site corresponded to a positively charged segment KRSN...RTVR(207-227), which also seemed to be necessary for receptor binding. We conclude that conformational changes in TC upon Cbl binding are accompanied by the convergence of multiple domains, and only the assembled conformation of the protein (i.e. holo-TC) has high affinity for the receptor.


Hormonal responses in ethanol-induced hypoglycemia.
Seven patients with clinical alcoholic hypoglycemia showed suppressed pretreatment plasma insulin levels and raised concentrations of somatotropin, hydrocortisone and pancreatic glucagon. A prolonged intravenous glucose infusion failed to elicit adequate insulin output and marked hyperglycemia supervened.


Developing leadership through action learning.
The authors discuss the use of action learning to help nurses based at Guy's and St Thomas' Hospital Trust develop clinical leadership skills.


Hypovolemic shock caused by delayed-onset superior gluteal artery rupture, successfully treated with arteriographic embolization.
Rupture of the superior gluteal artery (SGA) is usually associated with pelvic bone fractures and acetabular fractures secondary to blunt trauma. However, despite recent advances in technologies and tools, rupture of the SGA remains a challenging problem because it is difficult to manage and is frequently associated with significantly high mortality and morbidity. We present a case of an 82-year-old man, who presented to our emergency department after a cultivator turnover accident and who showed stable initial vital signs and manifested only as blunt buttock traumatic contusion without any pelvic bone or acetabular fracture, which resulted in delayed massive bleeding from the SGA on eight days after trauma. A hypovolemic shock and abrupt 4.2 g/dl hemoglobin decrease caused by massive bleeding from delayed-onset SGA rupture, was successfully treated with urgent angiographic embolization. A delayed SGA bleeding should be considered in late-onset shock associated with blunt buttock trauma. Furthermore, early detection and embolization not only prevent further complications, such as compartment syndrome and hypovolemic shock, but also eliminate the need for any surgical interventions.


Anomaly prediction of CT equipment based on IoMT data.
Large-scale medical equipment, which is extensively implemented in medical services, is of vital importance for diagnosis but vulnerable to various anomalies and failures. Most hospitals that conduct regular maintenance have been suffering from medical equipment-related incidents for years. Currently, the Internet of Medical Things (IoMT) has emerged as a crucial tool in monitoring the real-time status of the medical equipment. In this paper, we develop an IoMT system of Computed Tomography (CT) equipment in the West China Hospital, Sichuan University and collected the system status time-series data. Novel multivariate time-series classification models and frameworks are proposed to predict the anomalies of CT equipment. The important features that are closely related to the equipment anomalies are identified with the model. We extracted the real-time CT equipment status time-series data of 11 equipment between May 19, 2020 and May 19, 2021 from the IoMT, which includes the equipment oil temperature, anode voltage, etc. The arcs are identified as labels of anomalies due to their relationship with decreased imaging quality and CT equipment failures. To improve prediction accuracy, the statistics and transformations of the raw historical time-series data segment in the sliding time window are used to construct new features. Due to the particularity of time-series data, two frameworks are proposed for splitting the training and test sets. Then the Decision Tree, Support Vector Machine, Logistic Regression, Naive Bayesian, and K-Nearest Neighbor classification models are used to classify the system status. We also compare our model to state-of-the-art models. The results show that the anomaly prediction accuracy and recall of our method are 79% and 77%, respectively. The oil temperature and anode voltage are identified as the decisive features that may lead to anomalies. The proposed model outperforms the others when predicting the anomalies of the CT equipment based on our dataset. The proposed method could predict the state of CT equipment and be used as a reference for practical maintenance, where unexpected anomalies of medical equipment could be reduced. It also brings new insights into how to handle non-uniform and imbalanced time series data in practical cases.


Biochemical characterization of H9/25, an allospecificity encoded by the Ly-6 region.
H9/25, an allospecificity encoded by the Ly-6 region, was biochemically characterized. It was sensitive to pepsin and heat treatment, but was resistant to periodate oxidation. Its apparent molecular weight was approximately 12000 daltons by gel filtration. The antigenic molecule was partially purified by gel filtration and antibody affinity chromatography. The partially purified antigen molecule was radioiodinated, immunoprecipitated with monoclonal antibody H9/25, and analyzed by SDS-polyacrylamide gel electrophoresis. The autoradiograph showed the molecular weight of H9/25 to be approximately 15000 daltons under reducing conditions. These results indicate that H9/25 is a protein with a single polypeptide chain of 12000-15000 daltons molecular weight, and the antigenic specificity is carried by a peptide but not a carbohydrate moiety.


Correlations between the clinical picture and the intentionality in schizophrenic and schizoaffective patients.
The results are presented of catamnestic research on 24 patients with the diagnosis of schizophrenia at the first clinical episode confirmed according to the ICD-10 criteria. The clinical picture rated with the Positive and Negative Symptoms Scale (Kay, Fiszbein and Opler, 1987) and with the BPRS, was correlated with the intentionality, which was rated with the InSka (IntentionalitätsSkala; Mundt, 1985). The transformation of the phenomenal significance into a numeric value enables the use of mathematical methods for the search of interactions inside the schizophrenic phenomenon. We found the following significant tendencies: (1) the negative syndrome score correlates with the residual intentionality; (2) the negative syndrome score correlates with the premorbid intentionality; (3) the clinical thought disturbance correlates with the premorbid speech content intentional profile.


Clock-talk: have we forgotten about geographic variation?
Wyeomyia smithii, the pitcher-plant mosquito, has evolved from south to north and from low to high elevations in eastern North America. Along this seasonal gradient, critical photoperiod has increased while apparent involvement of the circadian clock has declined in concert with the evolutionary divergence of populations. Response to classical experiments used to test for a circadian basis of photoperiodism varies as much within and among populations of W. smithii as have been found in the majority of all other insects and mites. The micro-evolutionary processes revealed within and among populations of W. smithii, programmed by a complex underlying genetic architecture, illustrate a gateway to the macro-evolutionary divergence of biological timing among species and higher taxa in general.


Anterior lumbar sagittal alignment after anterior or lateral interbody fusion.
Anterior or lateral interbody fusion is a treatment option for lumbar disc disease. A segmental change occurs after such surgery. This study was designed to evaluate the changes in the lumbar regional alignment after a single or two-level standalone anterior or lateral interbody fusion (ALIF or LLIF). Data from patients referred to our institution between March 2013 and November 2015 for standalone ALIF or LLIF for low-grade isthmic spondylolisthesis or degenerative discopathy were retrospectively included in our analysis. Patients with a history of spinal fusion were excluded. Global and regional alignments were analyzed pre- and postoperatively. Pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), lumbar lordosis (LL), index segmental lordosis (ISL) and L4S1 lordosis were compared. Three groups according to the pelvic incidence (PI) (low, normal and high) were separately analyzed then compared. Forty-one women and 27 men (mean age was 46 years; range 25-66) were included. The mean follow-up was 10.8 (range 3-34 months). The patients were globally well balanced preoperatively and remained after surgery (SVA stagnated from 16.76±28.42mm to 15.97±28.20mm, P=0.75). PT and LL did not vary. L4S1 lordosis, and ISL were significantly increased respectively from 30.56±8.59 to 34.58±7.47 (P=0.0026) and from 5.94±5.25 to 12.99±5.87 (P<0.0001) at latest follow-up. Despite effective changes in the segmental lordosis at the index levels, our findings suggest that one or two-levels standalone ALIF or LLIF had no effect on the global balance and the lumbar lordosis. The three groups behaved similarly, the regional lordosis was redistributed in a better harmony (L4S1/LL ratio went up from 55% to 61%, P=0.01). Retrospective study. 4.


Does fixity affect prognosis in colorectal tumours?
In a retrospective series of 301 colorectal tumours, tumour fixity was assessed, and was found to be of prognostic significance in relation to 5-year survival. Fixity of the tumour was associated with low curative resection rate and advanced tumour state. Fixation did not correlate significantly with the site or differentiation of the tumour nor with operative mortality.


Dechlorination of chloral hydrate is influenced by the biofilm adhesin protein LapA in Pseudomonas putida LF54.
LapA is the largest surface adhesion protein of Pseudomonas putida that initiates biofilm formation. Here, by using transposon insertion mutagenesis and a conditional lapA mutant, we demonstrate for the first time that LapA influences chloral hydrate (CH) dechlorination in P. putida LF54.


Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight/obese postmenopausal women.
In obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. Thirty in total, overweight/obese postmenopausal women, were included in the study: 15 with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30 min intervals, leptin, sOB-R, adiponectin and resistin at 60 min intervals during the 120 min OGTT. In fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. In overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.


About a rare ankle injury in adults: Case report of a Tillaux fracture in adult.
Tillaux fracture occurs as a result of a forced external rotation mechanism involving the anterolateral tibial plafond. The occurrence of this fracture in adults is rare because the ligament usually disrupts before causing bone avulsion. We report the case of a 31-year-old man who, following a trauma in a foot-ball game, was admitted for management of an isolated anterolateral tibial plafond fracture. The diagnosis was made by X-ray, supported by CT scan, which investigated the fracture and excluded other associated injuries. Management was based on open reduction and direct screw fixation. After a 12-month follow-up, we obtained an excellent result. Tillaux fracture occurs most often in adolescents, more rarely in adults. The balance between ligament strength and bone strength explains the occurrence of this fracture in children, and the decrease in its incidence with the closure of the conjugation cartilage. Diagnosis is based on a complete radiological workup with standard radiographs and possibly a CT scan. Treatment is most often surgical using either direct screw fixation or plate osteosynthesis. Avulsion of the anterolateral distal tibia, called Tillaux fracture, is a rare entity requiring careful examination and a complete assessment in order to make the diagnosis and to eliminate other associated injuries. Although the literature reports single cases, management is often surgical.


Efficacy of ultrasound-guided erector spinae plane block on postoperative quality of recovery and analgesia after modified radical mastectomy: randomized controlled trial.
Erector spinae plane block (ESPB) is a novel regional anesthesia technique that is gaining popularity for postoperative pain management. This randomized controlled trial evaluated the effect of ESPB on quality of recovery (QoR) in patients undergoing modified radical mastectomy. Eighty-two female patients undergoing modified radical mastectomy were included. Patients were randomly assigned to receive preoperative ultrasound-guided ESPB with either 0.5% ropivacaine or saline. The primary outcome was QoR, assessed 24 hours postoperatively using the 15-item QoR questionnaire (QoR-15). Secondary outcomes included postoperative pain scores, postoperative cumulative opioid consumption, postanesthesia care unit (PACU) discharge time, postoperative nausea or vomiting and dizziness. Global QoR-15 scores 24 hours postoperatively were significantly higher (indicating better quality) in the ESPB group (median 120, IQR 118-124) compared with the control group (median 110, IQR 108.3-112.8), with a median difference of 10 (95% CI 9 to 12, p<0.001). Compared with the control group, ESPB with ropivacaine reduced pain scores up to 8 hours after surgery, as well as reduced postoperative cumulative opioid consumption and PACU discharge time. A single preoperative injection of ESPB with ropivacaine may improve QoR postoperatively and acute postoperative analgesia in patients undergoing a modified radical mastectomy. ChiCTR-1800019599.


Epigenetics and the modulation of neuroinflammation.
Innate immune responses in the central nervous system (CNS) have key roles influencing both physiological and pathological processes. Microglia are innate immune effector cells that reside within the CNS. These inflammatory cells are constantly surveying their external environment and rapidly respond to a variety of molecules that signal changes in CNS homeostasis. In response to these signals, microglia influence neuronal connections, modulate the functions of other glia, and mediate inflammatory responses to disease or injury. In parallel with the regulation of inflammatory responses outside of the CNS, investigators have observed that microglia are capable of heterogeneous responses to exogenous and endogenous signals. While much of this molecular and morphological heterogeneity is regulated by gene transcription, there is ample evidence that microglial behavior is determined, in part, by epigenetic regulation. Recent work has demonstrated that processes involving DNA methylation, histone modification, and noncoding RNAs also have important roles in modulating neuroinflammation. Here I will review the evidence supporting a role for epigenetic regulation of neuroinflammation and describe how this might influence the outcome of several CNS disorders, including addiction, infection, multiple sclerosis, and stroke.


Study of the Relationship between Haze Performance and Fractal Dimension in Micro-Sized Segregated Liquid Crystals Embedded in a Polymer Matrix Consisting of a Thiol-ene Prepolymer and a Multi-Functional Acrylate.
Micro-sized segregated liquid crystals (MSLCs) surrounded by a polymer medium can be used for haze film applications. When incident light passes through the MSLC film, the microsized particles act as light scattering centers. In this study, the results of the addition of a multi-functional acrylate to a commercial thiol-ene prepolymer system, as well as the morphology of (LC) droplets, fractal dimension (D), and the optical haze performance of the micro-sized segregated LCs formed by UV-initiated photopolymerization, are reported. With increasing fraction of the multi-functional acrylate within the host polymer matrix, the small scattering centers (LC droplets) also increase, giving rise to a large optical haze in the prepared film. The optical haze can be characterized by the D of the associated LC droplet morphology in the films. The optical haze and D exhibit a strong correlation; thus, a qualitative prediction of the optical haze is possible via geometric fractal analysis.


RAST atopy screen.
A single in vitro screening test for atopic allergy is described. It uses the radioallergosorbent test (RAST) principle, and has been applied to screening sera from U.K. patients with possible atopic symptoms. When compared with the Phadebas RAST, the test sensitivity was 97% and the specificity 100%, and these results suggest that it is useful in any preliminary allergy investigation.


Solubilization of 2',3'-cyclic nucleotide 3'-phosphohydrolase from bovine brain without detergents.
The enzyme in brain that hydrolyzes 2',3'-cyclic nucleotides to the 2'-mononucleotides has been found by several authors to be concentrated in the myelin fraction. To facilitate further study of the enzyme, one of our objectives has been to develop a method of solubilizing the enzyme without the use of detergents. When an acetone powder from brain white matter is homogenized with 1 M guanidinium chloride in 0.2 M buffer at pH 6, 10(-3) M in EDTA and in dithiothreitol, the enzyme is solubilized. If the guanidinium chloride is removed by dialysis in a single step, the enzyme reprecipitates, but if a fractional precipitation is performed by reducing the guanidinium chloride concentration by dilution, the enzyme remains in solution at 0.2 M guanidinium chloride. The precipitates obtained in this fractionation probably contain constituents which, at low salt concentration, formed a part of an insoluble aggregate, since after removal of the pellet the supernatant solution can be dialyzed free of guanidinium chloride without precipitating the enzymic activity. The enzyme thus prepared remains in the supernatant when centrifuged at 108,000 X g for 3 h and can be submitted to (NH4)2SO4 fractionation and chromatography on carboxymethyl-Sephadex and on hydroxylapatite. The enzyme has thereby been purified 200-fold in about 20% yield.


Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.
There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder.


Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides.
Oxidative stress has many effects on biological cells, including the modulation of gene expression. Reactive oxygen species are known to up-regulate and down-regulate RNA expression in prokaryotic and eukaryotic cells. We have previously reported that a preferential and calcium-dependent down-regulation of mitochondrial RNAs occurs when HA-1 hamster fibroblasts are exposed to hydrogen peroxide. Here we extend these studies to determine whether this down-regulation is specific to mitochondria RNA or involves general polynucleotide degradation. Degradation and associated decreases in the levels of 16S mitochondrial rRNA following exposure of cells to 400 microM hydrogen peroxide were found to be dependent on calcium at 2 and 5 h. Degradation of mitochondrial genomic DNA was also observed following peroxide exposure, and occurred at similar time points as for mitochondrial RNA degradation. As with mitochondrial RNA degradation, this mitochondrial genomic DNA degradation was dependent on calcium. These results indicate that there is a general, calcium-dependent degradation of mitochondrial polynucleotides following exposure of HA-1 fibroblasts to oxidative stress, and suggest that a dramatic shut-down in mitochondrial biosynthesis is an early-stage response to oxidative stress.


Emotional environments retune the valence of appetitive versus fearful functions in nucleus accumbens.
The nucleus accumbens mediates both appetitive motivation for rewards and fearful motivation toward threats, which are generated in part by glutamate-related circuits organized in a keyboard fashion. At rostral sites of the medial shell, localized glutamate disruptions typically generate intense appetitive behaviors in rats, but the disruption incrementally generates fearful behaviors as microinjection sites move more caudally. We found that exposure to stressful environments caused caudal fear-generating zones to expand rostrally, filling approximately 90% of the shell. Conversely, a preferred home environment caused fear-generating zones to shrink and appetitive-generating zones to expand caudally, filling approximately 90% of the shell. Thus, the emotional environments retuned the generation of motivation in corticolimbic circuits.


Association of blood pressure trajectories with coronary heart disease among the disabled population in Shanghai, China: a cohort study of 7 years following up.
Much less is known about the importance of blood pressure (BP) trajectories concerning the incidence of coronary heart disease (CHD) in people with disabilities. Our aim was to evaluate this association. This cohort study surveyed 5711 adults from the Shanghai Disability Health Survey from June 2012 to June 2019. The latent class growth mixture model was used to examine distinct BP trajectories. We evaluated the association of BP trajectories with the risk of CHD by Cox proportional hazard models. The model for CHD risk fitted to BP trajectories was compared with models fitted to other BP-related indicators by goodness-of-fit, discrimination, and calibration. During a median follow-up of 71.74 months, 686 cases (median age was 49.03 (54.49, 58.55) years, 51.90% female) with CHD were identified, with a cumulative incidence of 12.01%. Systolic BP (SBP) and diastolic BP (DBP) were categorized into three classes, respectively. A statistically significant association was only observed between SBP trajectories and CHD. Compared with the normotensive stable SBP group (n = 1956), the prehypertension-stable group (n = 3268) had a higher risk (adjust hazards ratio (aHR) = 1.266, 95% confidence interval (CI) 1.014-1.581), and the stage 1 hypertension-decreasing group (n = 487) had the highest risk (aHR = 1.609, 95%CI 1.157-2.238). Among the BP-related indicators, the SBP trajectory was the strongest predictor of new-onset CHD. Findings were similar when sensitivity analyses were conducted. SBP trajectory was a more important risk factor for CHD than other BP-related indicators and stringent BP control strategies may be effective for primary CHD prevention in the disabled population.


Efficacy and safety of Chinese herbal medicine Buzhong Yiqi decoction for postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis.
Postmenopausal osteoporosis (PMOP) is a disorder of bone metabolism caused by estrogen deficiency in women after menopause, which manifests clinically as pain, spinal deformities, and even fragility fractures, affecting the quality of life of patients and possibly shortening their life span. Traditional Chinese medicine prescription Buzhong Yiqi Decoction (BZYQD) has been widely used in clinical practice and achieved good results. But there is no high-level evidence to support this result. The aim of this study is to evaluate BZYQD's efficacy and safety in the management of PMOP. We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure, Wanfang Data, Chinese Scientific Journals Database, Chinese databases SinoMed, PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction on language and status, the time from the establishment of the database to September 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. This study will evaluate the efficacy and safety of BZYQD in the treatment of PMOP, to provide high-quality, evidence-based clinical recommendations. The study provides a trustable clinical foundation for BZYQD in the treatment of PMOP.


Generation of Chimeras from Porcine Induced Pluripotent Stem Cells.
Pig induced pluripotent stem cells (piPSCs) offer a great opportunity and a number of advantages in the generation of transgenic animals. These immortalized cells can undergo multiple rounds of genetic modifications (e.g., gene knock-in, knockout) and selection leading to animals that have optimized traits of biomedical or agricultural interests. In this chapter we describe the production and characterization of piPSCs, microinjection of piPSCs into embryos, embryo transfer and production of chimeric animals based on successful protocols.


Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.
Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.


Association of vitamin D receptor gene polymorphisms with hypercalcemia in peritoneal dialysis patients.
Some polymorphisms at the human vitamin D receptor (VDR) gene locus may influence calcium and bone metabolism. We investigated the roles of the BsmI and TaqI VDR gene polymorphisms in the development of hypercalcemia in Turkish peritoneal dialysis (PD) patients. We enrolled 132 PD patients treated with dialysate containing 1.75 mmol/L calcium. Serum levels of calcium, phosphorus, albumin, and intact parathyroid hormone (iPTH), and the cumulative doses of calcium-based phosphate binders and calcitriol were recorded every 3 months. The VDR BsmI and TaqI genotypes were determined by polymerase chain reaction. When the patients were categorized according to these VDR genotypes, serum levels of phosphorus and iPTH and cumulative doses of calcium-based phosphate binders and calcitriol were similar across groups. The corrected serum calcium levels tended to increase in the patients with BsmI non-BB (Bb + bb) variants, but were significantly decreased in the BB variants (9.9 +/- 0.7 vs 9.1 +/- 0.6 mg/dL, p < 0.05). Hypercalcemia appeared in 21.2% of the patients during the follow-up period. The hypercalcemic patients had a significantly higher prevalence of the BsmI non-BB genotype than the normocalcemic patients (85.7% vs 59.6%, p < 0.007). On the contrary, the serum calcium levels were not affected by the TaqI VDR gene polymorphism (p > 0.05). These findings suggest that the non-BB variants of the BsmI VDR gene polymorphism are associated with increased risk of developing hypercalcemia in PD patients.


Measurement of the CRAC Channel Fast Ca2+-Dependent Inactivation (FCDI).
Fast Ca2+-dependent inactivation (FCDI) is a safety mechanism limiting Ca2+ entry through some types of Ca2+ channels, including Ca2+ release-activated Ca2+ (CRAC) channels. This type of inactivation is caused by Ca2+, which passes through Ca2+ channel and binds to a specific site within a short distance from the inner mouth of the pore, causing channel to shut.The main technique that is used to investigate FCDI is whole-cell patch clamping. Since the cloning of the molecular components of the CRAC channel, STIM1 and Orai1, FCDI of CRAC channel has been studied using HEK293T heterologous expression system. In this paper we describe a method of quantifying CRAC channel FCDI by using instantaneous tail currents.


Outcome of segmental gastrectomy versus distal gastrectomy for early gastric cancer.
Because of the frequent occurrence of postgastrectomy disturbances after distal gastrectomy (DG), segmental gastrectomy (SG) has recently been applied to early gastric cancer (EGC). Outcomes of SG and DG in patients with EGC were compared to clarify the usefulness of SG as a treatment for EGC. This retrospective study involved 61 patients with EGC: 28 patients who underwent DG before March 1996 and 33 patients who underwent SG after April 1996 during the period April 1991 through March 2002. Patient and tumor characteristics, operative results, and postoperative outcomes were compared between the two groups. The postoperative/preoperative body weight ratio was higher in the SG group than in the DG group. Early dumping syndrome and reflux gastritis occurred less frequently after SG than after DG. The incidence of postoperative complications was similar in the two groups. All patients remained alive without recurrence during a mean follow-up period of 54.7 months in the SG group and 99.9 months in the DG group. In comparison to DG, SG is associated with improved postoperative quality of life with no decrease in operative curability of EGC. Thus, SG is a feasible treatment for EGC.


Epidemiology of selenium and type 2 diabetes: can we make sense of it?
The potential of some selenoproteins to protect against oxidative stress led to the expectation that selenium would be protective against type 2 diabetes, and indeed in early in vivo and in vitro studies, selenium (as selenate) was shown to have antidiabetic and insulin-mimetic effects. However, more recently, findings from observational cross-sectional studies have raised concern that high selenium exposure may be associated with type 2 diabetes or insulin resistance, at least in well-nourished populations, though trial results have been inconsistent. Moreover, the largest trials that investigated the effects of selenium supplementation on diabetes endpoints have had cancer prevention as their primary outcome, casting doubt on the interpretation of posthoc analyses. Factors affecting serum/plasma selenium are not just location and level of disease-associated inflammation but the fact that higher concentrations of plasma selenoprotein P yet lower concentrations of glutathione peroxidase are found in type 2 diabetic patients than in normal subjects. From a public health perspective, selenium is marketed as a dietary supplement and is commonly added to multivitamin/mineral preparations that are consumed in many Western countries. Based on current evidence, however, the indiscriminate use of selenium supplements in individuals and populations with adequate-to-high selenium status cannot be justified and may increase risk. In conclusion, although there is a clear link between certain selenoproteins and glucose metabolism or insulin resistance, the relationship between selenium and type 2 diabetes is undoubtedly complex. It is possible that the relationship is U-shaped, with possible harm occurring both below and above the physiological range for optimal activity of some or all selenoproteins.


Modulation of diverse oncogenic signaling pathways by oroxylin A: An important strategy for both cancer prevention and treatment.
Regardless of major advances in diagnosis, prevention and treatment strategies, cancer is still a foreboding cause due to factors like chemoresistance, radioresistance, adverse side effects and cancer recurrence. Therefore, continuous development of unconventional approaches is a prerequisite to overcome foregoing glitches. Natural products have found their way into treatment of serious health conditions, including cancer since ancient times. The compound oroxylin A (OA) is one among those with enormous potential against different malignancies. It is a flavonoid obtained from the several plants such as Oroxylum indicum, Scutellaria baicalensis and S. lateriflora, Anchietea pyrifolia, and Aster himalaicus. The main purpose of this study is to comprehensively elucidate the anticancerous effects of OA against various malignancies and unravel their chemosensitization and radiosensitization potential. Pharmacokinetic and pharmacodynamic studies of OA have also been investigated. The literature on antineoplastic effects of OA was searched in PubMed and Scopus, including in vitro and in vivo studies and is summarized based on a systematic review protocol prepared according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The term "oroxylin A" was used in combination with "cancer" and all the title, abstracts and keywords appeared were considered. In Scopus, a total of 157 articles appeared out of which 103 articles that did not meet the eligibility criteria were eliminated and 54 were critically evaluated. In PubMed, from the 85 results obtained, 26 articles were eliminated and 59 were included in the preparation of this review. Mounting number of studies have illustrated the anticancer effects of OA, and its mechanism of action. OA is a promising natural flavonoid possessing wide range of pleiotropic properties and is a potential anticancer agent. It has a great potential in the treatment of multiple cancers including brain, breast, cervical, colon, esophageal, gall bladder, gastric, hematological, liver, lung, oral, ovarian, pancreatic and skin. However, lack of pharmacokinetic studies, toxicity assessments, and dose standardization studies and adverse effects limit the optimization of this compound as a therapeutic agent.


The non-federal healthcare sector meets NIMS and NIPP: evolving roles and responsibilities for healthcare safety and security.
The authors spell out what the Department of Homeland Security and the Department of Health and Human Services, and other federal agencies are doing to get the healthcare industry much more involved in preventing, protecting and responding to future terrorist attacks and other disasters.


Substrate dynamics in enzyme action: rotations of monosaccharide subunits in the binding groove are essential for pectin methylesterase processivity.
The dynamical behavior of biomacromolecules is a fundamental property regulating a large number of biological processes. Protein dynamics have been widely shown to play a role in enzyme catalysis; however, the interplay between substrate dynamics and enzymatic activity is less understood. We report insights into the role of dynamics of substrates in the enzymatic activity of PME from Erwinia chrysanthemi, a processive enzyme that catalyzes the hydrolysis of methylester groups from the galacturonic acid residues of homogalacturonan chains, the major component of pectin. Extensive molecular dynamics simulations of this PME in complex with decameric homogalacturonan chains possessing different degrees and patterns of methylesterification show how the carbohydrate substitution pattern governs the dynamics of the substrate in the enzyme's binding cleft, such that substrate dynamics represent a key prerequisite for the PME biological activity. The analyses reveal that correlated rotations around glycosidic bonds of monosaccharide subunits at and immediately adjacent to the active site are a necessary step to ensure substrate processing. Moreover, only substrates with the optimal methylesterification pattern attain the correct dynamical behavior to facilitate processive catalysis. This investigation is one of the few reported examples of a process where the dynamics of a substrate are vitally important.


Divergence in social traits in Trinidadian guppies selectively bred for high and low leadership in a cooperative context.
In many animal species, individuals with certain morphological, physiological, or behavioural traits may have a disproportionately large role in determining group behaviour. While most empirical studies of leadership have focused on behaviour of individuals exploring new environments or foraging, little is known about leading behaviour in other ecological contexts. Here, we use a selective breeding design in the Trinidadian guppy (Poecilia reticulata) to quantify the heritability of leadership in a cooperative context, and determine the behavioural traits associated with it. Firstly we found that phenotypic selection for high and low leadership (HL and LL, respectively) over three filial generations resulted in pronounced differences in leadership tendency with a moderate degree of heritability. In our assay of other social traits, LL males were more aggressive and sampled their social environment less than HL males, but HL and LL females did not differ in either aggressiveness or sociability. Traits such as boldness and exploratory tendency did not diverge between the two lines. Leading behaviour was thus associated with social traits in males, but not females; suggesting that there may be sex-specific mechanisms driving the emergence of leadership in this context. We discuss our findings in the context of the evolution of cooperation.


Differences in Brain Adaptive Functional Reorganization in Right and Left Total Brachial Plexus Injury Patients.
Total brachial plexus avulsion injury (BPAI) results in the total functional loss of the affected limb and induces extensive brain functional reorganization. However, because the dominant hand is responsible for more cognitive-related tasks, injuries on this side induce more adaptive changes in brain function. In this article, we explored the differences in brain functional reorganization after injuries in unilateral BPAI patients. We applied resting-state functional magnetic resonance imaging scanning to 10 left and 10 right BPAI patients and 20 healthy control subjects. The amplitude of low-frequency fluctuation (ALFF), which is a resting-state index, was calculated for all patients as an indication of the functional activity level of the brain. Two-sample t-tests were performed between left BPAI patients and controls, right BPAI patients and controls, and between left and right BPAI patients. Two-sample t-tests of the ALFF values revealed that right BPAIs induced larger scale brain reorganization than did left BPAIs. Both left and right BPAIs elicited a decreased ALFF value in the right precuneus (P < 0.05, Alphasim corrected). In addition, right BPAI patients exhibited increased ALFF values in a greater number of brain regions than left BPAI patients, including the inferior temporal gyrus, lingual gyrus, calcarine sulcus, and fusiform gyrus. Our results revealed that right BPAIs induced greater extents of brain functional reorganization than left BPAIs, which reflected the relatively more extensive adaptive process that followed injuries of the dominant hand.


Derivation of a clinical guideline for the assessment of nonspecific abdominal pain: the Guideline for Abdominal Pain in the ED Setting (GAPEDS) Phase 1 Study.
The purpose of this study was to identify a clinical guideline for the evaluation of nonspecific abdominal pain (NSAP) using history, physical examination, laboratory analysis, acute abdominal series (AAS) radiographs, and nonenhanced helical computed tomography (NHCT) clinical predictor variables (CPVs). The setting of this study was at an urban emergency department (ED) with 70,000 yearly visits. This is an institutional review board-approved, prospective, observational study. The primary outcome variable was urgent intervention (UI), defined as a diagnosis requiring surgical or medical treatment to prevent death or major morbidity. Subjects underwent prompted history, physical, laboratory studies, AAS, and NHCT and were followed up to 6 months for ultimate diagnosis and outcome. CPVs were subjected to classification and regression tree analysis. One hundred sixty-five subjects were analyzed. Thirteen percent of subjects required UI within 24 hours of presentation; an additional 34% underwent elective interventions that mitigated morbidity or mortality. Four guideline models were generated. Model 1 consisted of history and physical, with a sensitivity of 25%, a specificity of 92%, a positive likelihood ratio of 3.17, and a negative likelihood ratio of 0.81. Model 2 consisted of model 1 with laboratory, with a sensitivity of 39%, a specificity of 88%, a positive likelihood ratio of 3.25, and a negative likelihood ratio of 0.69. Model 3 consisted of model 2 with AAS, with a sensitivity of 56%, a specificity of 81%, a positive likelihood ratio of 2.94, and a negative likelihood ratio of 0.54. Model 4 comprised all inputs, including NHCT, with a sensitivity of 92%, a specificity of 90%, a positive likelihood ratio of 9.2, and a negative likelihood ratio of 0.089. NHCT was the single most accurate CPV for UI. No clinical guideline was identified exclusive of NHCT that possessed adequate sensitivity for exclusion of UI. NHCT is a rational choice for decision support in the evaluation of NSAP and is likely the single most useful diagnostic adjunct available to augment the clinical evaluation.


Reproductive consequences of EDCs in birds: what do laboratory effects mean in field species?
The varied reproductive strategies of birds present a challenge in developing reliable indices for the assessment of effects of endocrine disrupting chemicals (EDCs). Precocial species, such as quail, appear to be most sensitive to EDC effects during embryonic development. Although the Japanese quail (Coturnix japonica) is a nonnative lab species, its reproductive strategy is similar to that of many free-ranging species. Because a great deal is known about the reproductive biology of this species and Japanese quail have a short generation time, this species is an ideal candidate for testing EDC effects. In this review, we present data collected in a two-generation design with embryonic exposure to estradiol benzoate (EB). This study was conducted to provide fundamental information for establishing reliable reproductive endpoints associated with estrogenic EDC exposure. Data were collected for a variety of endpoints, which were chosen as measures of reproductive capability and success. These reproductive fitness measures included fertility, hatching success, and offspring viability. Endocrine measures consisted of plasma hormone levels and gonad weight/condition. Neuroendocrine systems, such as the monoamine neurotransmitter systems, regulate hypothalamic gonadotropin releasing hormone (GnRH) and reproductive behavior. Therefore, these variables should potentially be very sensitive indicators. Behavioral measures included reproductive behavior. Results showed that embryonic estradiol exposure affected endocrine and behavioral responses in males and impacted productivity in females. Therefore, quails provide an excellent model to determine fundamental actions of EDCs. The laboratory trials then serve as a basis for the extrapolation of findings of controlled laboratory studies to effects that may be observable in free-ranging species.


Curating Cyberbullying Datasets: a Human-AI Collaborative Approach.
Cyberbullying is the use of digital communication tools and spaces to inflict physical, mental, or emotional distress. This serious form of aggression is frequently targeted at, but not limited to, vulnerable populations. A common problem when creating machine learning models to identify cyberbullying is the availability of accurately annotated, reliable, relevant, and diverse datasets. Datasets intended to train models for cyberbullying detection are typically annotated by human participants, which can introduce the following issues: (1) annotator bias, (2) incorrect annotation due to language and cultural barriers, and (3) the inherent subjectivity of the task can naturally create multiple valid labels for a given comment. The result can be a potentially inadequate dataset with one or more of these overlapping issues. We propose two machine learning approaches to identify and filter unambiguous comments in a cyberbullying dataset of roughly 19,000 comments collected from YouTube that was initially annotated using Amazon Mechanical Turk (AMT). Using consensus filtering methods, comments were classified as unambiguous when an agreement occurred between the AMT workers' majority label and the unanimous algorithmic filtering label. Comments identified as unambiguous were extracted and used to curate new datasets. We then used an artificial neural network to test for performance on these datasets. Compared to the original dataset, the classifier exhibits a large improvement in performance on modified versions of the dataset and can yield insight into the type of data that is consistently classified as bullying or non-bullying. This annotation approach can be expanded from cyberbullying datasets onto any classification corpus that has a similar complexity in scope.


An ecological perspective for understanding regional integration based on ecosystem service budgets, bundles, and flows: A case study of the Jinan metropolitan area in China.
Regional integration can contribute to co-occurring benefits of different parts of an urban agglomeration by managing these parts as a whole. However, current regional integration mainly focuses on the socioeconomic rather than the ecological dimension. To interpret regional ecological integration, we firstly selected six typical ecosystem services (ESs) to represent ecological benefits that potentially need to be improved by ecological integration for further analysis. Then we used ES budgets, bundles, and flows to investigate the potential, basic analysis unit, and occurring manners of ecological integration, respectively. Our results show that supply-demand mismatches were observed in all the ES types. Meanwhile, coexisting ES surpluses and deficits on the town scale were found in supporting biodiversity, soil retention, water yield, green space recreation, and crop yield, which indicates that their supply-demand mismatches can be mitigated with ecological integration. Furthermore, all the towns were classified into five spatial clusters with distinct ES budget bundles, which acted as the basic analysis unit of ecological integration. ES flows with three flow characteristic types were observed between different clusters, and all the clusters had ES provider-beneficiary relationships with each other. Based on the ES approach, we provided an ecological perspective for understanding regional integration, which has the potential to promote regional ecological sustainability.


Oxidized cellulose-based reaction mimicking thyroidal recurrence of disease: a case report and literature review.
Oxidized cellulose is a hemostatic agent currently used in surgery. Foreign body reactions have been described after its use. This paper describes a foreign body reaction caused by oxidized cellulose in a young woman who underwent thyroid surgery. A patient underwent two thyroid surgeries for treatment of papillary carcinoma. Five years after the last surgery, an asymptomatic mass was detected with a routine ultrasound in the left thyroid cavity. After surgical removal, the mass turned out to be a foreign body granuloma based on oxidized cellulose sheets used in the previous surgery. The patient was discharged from the hospital without complications. The follow-up period was uneventful. Oxidized cellulose is a useful tool in surgery to control and prevent intra and post-operative bleeding. Even if it is a biodegradable material, sometimes it persists in the human body causing foreign body reactions that can be misdiagnosed. The online version contains supplementary material available at 10.1007/s12070-023-03556-0.


Anti-JAM-C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma.
Junctional adhesion molecule (JAM)-C is a member of the JAM family, expressed by a variety of different cell types, including human B lymphocytes and some B-cell lymphoma subtypes-in particular, mantle cell lymphoma (MCL). Treatment with anti-JAM-C pAbs reduces homing of human B cells to lymphoid organs in a NOD/SCID mouse model. In the present study, the role of JAM-C in the engraftment of human lymphoma B cells in mice was investigated. Administration of novel anti-JAM-C mAbs reduced tumor growth of JAM-C+ MCL cells in bone marrow, spleen, liver, and lymph nodes of mice. Treatment with anti-JAM-C antibodies significantly reduced the proliferation of JAM-C-expressing lymphoma B cells. Moreover, the binding of anti-JAM-C antibodies inhibited the phosphorylation of ERK1/2, without affecting other signaling pathways. The results identify for the first time the intracellular MAPK cascade as the JAM-C-driven signaling pathway in JAM-C+ B cells. Targeting JAM-C could constitute a new therapeutic strategy reducing lymphoma B-cell proliferation and their capacity to reach supportive lymphoid microenvironments.


Levetiracetam in children with refractory status epilepticus.
The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.


Intranasal delivery of Borneol/R8dGR peptide modified PLGA nanoparticles co-loaded with curcumin and cisplatin alleviate hypoxia in pediatric brainstem glioma which improves the synergistic therapy.
Cisplatin (cis) is a first-line chemotherapeutic used for the treatment of intractable pediatric brainstem glioma (PBSG). Its therapeutic effect in PBSG is, however, critically challenged by the hypoxic microenvironment of the tumor and the presence of the blood brain barrier (BBB). Herein, we report on the intranasal administration of borneol (Bo)/R8dGR peptide modified PLGA based nanoparticles (NP) co-loaded with curcumin and cisplatin (cur/cis). We observed that borneol modification improved the brain penetration of the nanoparticles by reduction of the expression of ZO-1 and occludin in nasal mucosa, while the R8dGR peptide modification allowed the targeting of the NP through the binding on integrin αvβ3 receptors which are present on PBSG cells. Following intranasal administration, BoR-cur/cis-NP attenuated hypoxia in the PBSG microenvironment and reduced angiogenesis, which prolonged survival of GL261-bearing PBSG mice. Therefore, intranasal administration of BoR-cur/cis-NP, which deeply penetrate PBSG, is an encouraging strategy to attenuate hypoxia which potentiates the efficacy of cisplatin in the treatment of PBSG.


Does self reflection and insight correlate with academic performance in medical students?
Medical students in academic difficulty are often described as lacking insight. The Self Reflection and Insight Scale (SRIS) is a tool for measuring insight which has been validated in medical students. We investigated whether self reflection and insight scores correlate with academic performance in Year 4 medical students from a six year undergraduate medical degree, and whether self reflection and insight changes after one year of clinical training. Self reflection and insight scores were measured in 162 students at the start of Year 4 at the University of Western Australia. Performance in end of year written and clinical exams was monitored and correlated with SRIS. Seventy of the students were surveyed again at the start of Year 5 to see if scores changed or were stable after one year of full time clinical training. We found no correlation between self reflection or insight and academic performance in written and clinical exams. There was a significant increase in recognition of the need for self reflection in Year 5 compared with Year 4. While no correlation was found between this measure of self reflection and insight with academic performance, there was an increase in students' recognition of the need for reflection after one year of clinical studies. This study is a valuable first step towards a potentially exciting research domain and warrants further longitudinal evaluation with larger cohorts of students using additional measures of achievement.


Partial purification, substrate specificity and regulation of alpha-L-glycerolphosphate dehydrogenase from Saccharomyces carlsbergensis.
alpha-L-Glycerolphosphate dehydrogenase (sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase, EC 22.214.171.124) from Saccharomyces carlsbergensis was purified 400-fold. The enzyme preparation is free of interfering activities, such as glyceraldehyde phosphate dehydrogenase, alcohol dehydrogenase, triose phosphate isomerase and glycerolphosphatase. At pH 7.0 it is specific for NADH (Km = 0.027 mM with 0.8 mM dihydroxyacetone phosphate) and dihydroxyacetone phosphate (Km = 0.2 mM with 0.2 mM NADH). Between pH 5.0 and 6.0 the enzyme functions with NADPH, but only at 7% of the rate with NADH. Various anions (I- greater than SO42- greater than Br- greater than Cl-) act as inhibitors competing with the substrate dihydroxyacetone phosphate. Inorganic phosphate (Ki = 0.1 mM), pyrophosphate and arsenate are strong inhibitors. The nucleotides ATP and ADP are also inhibitory, but their action seems to be of the same type as the general anion competition (Ki = 0.73 mM for ATP). The results are consistent with the notion that the enzyme may regulate the redox potential of the NAD+/NADH couple during fermentation.


Children of Armageddon. Common developmental threats in high-conflict divorcing families.
This article traces how parental vulnerability to the feelings of humiliation and loss (inherent in highly conflicted divorce and custody litigation) distorts parenting capacities and parent-child relationships in distinctive ways, putting children at risk for specific kinds of developmental difficulties. Pre-oedipal children often fail to achieve a complete separation from their primary caretakers. Oedipal children, already struggling with separation issues, manifest sexualized anxiety and discomfort with gender identity. By latency, these children present as fragmented within themselves and in relationships with others. Each stage-specific response is discussed and illustrated. It is argued that mental health and legal professionals can use this in-depth understanding of child responses to help parents reframe their disputing agendas in terms of the child's developmental concerns and preoccupations to produce custody settlements that are more protective of the child's best interests.


Evaluation of the JT and corrected JT intervals as a new ECG method for monitoring doxorubicin cardiotoxicity in the dog.
A comparison was made of the sensitivity of ECG, ultrastructural heart pathology, and plasma enzymes CK-MB and alpha-HBDH as methods to assess doxorubicin cardiotoxicity in adult beagle dogs given doxorubicin 30 mg/m2 i.v. once a week for three times. A progressive increase in JT and QT intervals, in corrected JT (JTc) and QT (QTc) intervals as well as a reduction in both T wave amplitude and RR duration, were observed in doxorubicin-treated dogs; the electrocardiogram (ECG) abnormalities were associated with doxorubicin-induced ultrastructural changes in cardiac tissue, consisting of dilation of the sarcoplasmic reticulum, multiform, flasklike invaginations of T-tubules containing electrondense material, and interruption of the junctional sarcoplasmic reticulum, which became more severe as the observation period progressed. On the contrary, doxorubicin treatment was associated with transient changes in plasma CK-MB and alpha-HBDH, which were unrelated to the severity of chronic cardiotoxicity. Overall results suggest that the monitoring of the ECG parameters related to the repolarization of the cardiac muscle, and particularly JT and JTc, might be regarded as a noninvasive method for the study of doxorubicin cardiotoxocity in the dog.


Future liver remnant hypertrophy rate in portal vein embolization before left trisectionectomy: a retrospective cohort study.
Reports on the future liver remnant (FLR) hypertrophy rate in patients undergoing portal vein embolization (PVE) before left trisectionectomy are sparse. This study aimed to assess the FLR hypertrophy rate in patients undergoing PVE before left trisectionectomy. Between January 2010 and June 2021, 30 patients (22 men and eight women; mean age, 65.7 years) underwent PVE, mainly using gelatin sponge, before left trisectionectomy. The preoperative diagnosis was cholangiocarcinoma in 28 patients and colorectal liver metastases in two patients. The FLR hypertrophy rate, increase in the FLR volume (FLRV) ratio (the ratio of the FLRV to the total liver volume), and complications were evaluated. The patients were further divided into two groups: one group of patients with left portal vein stenosis or occlusion before PVE (n = 12) and another without left portal vein stenosis or occlusion before PVE (n = 18). The FLR hypertrophy rate and increase in the FLRV ratio were compared between the two groups. The FLR hypertrophy rate and increase in the FLRV ratio were 31.3% and 6.9%, respectively. One major complication, cholangitis, developed; however, its association with PVE was unclear. The difference in the FLR hypertrophy rate and the increase in the FLRV ratio between the two groups of patients was statistically insignificant. PVE before left trisectionectomy is effective in achieving FLR hypertrophy. PVE before left trisectionectomy was equally effective in patients with left portal vein stenosis or occlusion as compared to those without. The complication rates were acceptable.


Potential application of postbiotics metabolites from bioprotective culture to fabricate bacterial nanocellulose based antimicrobial packaging material.
Postbiotics (P) of FreshQ, a food protective culture, was prepared and used to develop an antimicrobial membrane by bacterial nanocellulose (BNC). Postbiotics were prepared in de Man, Rogosa and Sharpe medium and freeze-dried. The chemical composition was investigated by GC-MS and the antibacterial activity of postbiotics on different bacterial and fungal strains was investigated. Finally, postbiotics were included in wet and lyophilized BNC by ex-situ method, and their antibacterial activity and FTIR specifications were studied. The GC-MS analysis of postbiotics revealed the presence of fatty acids, alkanes, aldehydes, hydrocarbones fatty acid esters, propionic acid, and certain antibacterial and antifungal compounds such as 2,4-Di-tert-butyl phenol and dotriacontane. Postbiotics revealed antibacterial activity on all investigated strains in a concentration-dependent manner and as the concentation decreased, there was a significant reduction in antimicrobial effects. The zone of inhibition for all bacterial pathogens exceeded 20 mm, then they were classified as "extremely sensitive microorganisms" to the postbiotics at 50 % concentration, while fungal strains revealed a lower zone of inhibition (<17 mm). The order of antimicrobial susceptibility was as follows: Listeria monocytogenes > Staphylococcus aureus > Escherichia coli > Salmonella Typhimurium > Aspergillus flavus > Penicillium citrinum. We also recognized that P-BNC in wet form has significant antimicrobial activity than lyophilized form due to the high adsorption capacity and open 3D structure of BNC in wet form. The fabricated material can serve as an antimicrobial membrane for food applications.


On the nature of social stress: production of a modern mythology.
In recent decades there has been increasing interest in the subject of stress and a proliferation of research into the contribution of stress as a cause of illness. This association has been widely popularized and now has an established position within the body of popular ideas about health and illness. Nevertheless, very little has been confidently established about the relationship between stress and illness. The precise nature of stress itself eludes definition and there is no consensus as to what it encompasses. There has been a confusion of the models of stress developed in the laboratory and those applied to society. Early laboratory research was modelled on 'mechanical' images of stress taken from contemporary physics and engineering. Since then the stress theory has been heavily psychologised, although it still relies for its validation on the physiological models with which it is fundamentally non-comparable. It is argued that stress is not something naturally occurring in the world, but a manufactured concept which has by now become a 'social fact'. As such it has direct implications for the ways in which people perceive their world and act within it. Stress has increasingly come to be regarded as an integral part of everyday experience. Although much of the attractiveness of the stress theory derives from its seeming to reduce the arbitrariness of suffering, it also carries with it a significant ideological component. This can serve as a means of organising and expressing a variety of ideas about the social order relating, for example, to issues of individual autonomy and responsibility, or to the ways in which society might be perceived as dangerous, repressive or pathogenic.


A Campus-Wide Investigation of Clicker Implementation: The Status of Peer Discussion in STEM Classes.
At the University of Maine, middle and high school teachers observed more than 250 university science, technology, engineering, and mathematics classes and collected information on the nature of instruction, including how clickers were being used. Comparisons of classes taught with (n = 80) and without (n = 184) clickers show that, while instructional behaviors differ, the use of clickers alone does not significantly impact the time instructors spend lecturing. One possible explanation stems from the observation of three distinct modes of clicker use: peer discussion, in which students had the opportunity to talk with one another during clicker questions; individual thinking, in which no peer discussion was observed; and alternative collaboration, in which students had time for discussion, but it was not paired with clicker questions. Investigation of these modes revealed differences in the range of behaviors, the amount of time instructors lecture, and how challenging the clicker questions were to answer. Because instructors can vary their instructional style from one clicker question to the next, we also explored differences in how individual instructors incorporated peer discussion during clicker questions. These findings provide new insights into the range of clicker implementation at a campus-wide level and how such findings can be used to inform targeted professional development for faculty.


Progenitor targeting by adult stem cells in Ciona homeostasis, injury, and regeneration.
In the ascidian Ciona intestinalis, oral siphon amputation activates adult stem cell niches in the branchial sac to divide and dispatch migratory progenitor cells to a regeneration blastema at the site of injury. This study shows that progenitor cells derived from branchial sac stem cell niches have roles in homeostasis, wound repair, and regeneration of the siphons and neural complex (NC). During homeostasis, progenitor cells targeted the pharyngeal stigmata to replace ciliated cells involved in filter feeding. After individual or double siphon amputations, progenitor cells specifically targeted the oral or atrial siphons or both siphons, and were involved in the replacement of siphon circular muscle fibers. After oral siphon wounding, progenitor cells targeted the wound sites, and in some cases a supernumerary siphon was formed, although progenitor cell targeting did not predict the induction of supernumerary siphons. Following NC ablation, progenitor cells specifically targeted the regenerating NC, and supplied the precursors of new brain and neural gland cells. The tissues and organs targeted by branchial sac stem cells exhibited apoptosis during homeostasis and injury. It is concluded that branchial sac progenitor cells are multipotent and show targeting specificity that is correlated with apoptosis during homeostatic growth, tissue repair, and regeneration.


The effect of indocyanine green-based photodynamic therapy on healthy fibroblast and keratinocyte cells.
Photodynamic therapy is a promising invention to treat infections and cancer where conventional treatments are insufficient and have many side effects. Photodynamic therapy is mainly emphasized as having minimal side effects on healthy cells during local applications, even so photosensitizer can accumulate in any cell and unwanted deaths may occur upon irradiation. This study focused on the degree of photodynamic action with indocyanine green against healthy cells, when it has phototoxic effects on pathogens. Healthy mouse skin fibroblast and human skin keratinocyte cells were exposed to energy densities of 84 and 252 J/cm2 with 4, 10, 25, 50,100, 125 and 150 μg/mL indocyanine green which have efficiently killed gram-positive and gram-negative pathogens. Cell Viability, Lipid Peroxidation and Live/Dead Cell Staining analysis were performed to assess the phototoxicity with defined parameters on the healthy cells. 84 J/cm2 energy density was quite safe for keratinocytes with indocyanine green concentrations ranging from 4 to 125 μg/mL. When 252 J/cm2 energy density was used, most of the keratinocytes were damaged with any photosensitizer concentration. Fibroblasts only tolerate these energy densities together with 4 and 10 μg/mL indocyanine green. Increasing photosensitizer concentrations resulted in high phototoxic effect on them. Photodynamic therapy applications, which destroy pathogens, may also kill healthy eukaryotic cells. While some energy densities are safe, but others cause serious mortality rate on fibroblasts and keratinocytes. Therefore, harm to healthy cells related to photodynamic therapy parameters should be minimized by the optimization of energy densities and photosensitizer concentration properly.


Primary mutations in calmodulin prevent activation of the Ca(++)-dependent Na+ channel in Paramecium.
Paramecium tetraurelia behavioral mutant cam12 displays a "fast-2" behavioral phenotype: it fails to respond to Na+ stimuli. Electrophysiologically, it lacks a Ca(++)-dependent Na+ current. Genetics and DNA sequencing showed the primary defect of cam12 to be in the calmodulin gene (Kink et al., 1990). To correlate calmodulin structure and function in Paramecium, we elucidated the primary structure of cam12 calmodulin. Peptide sequencing confirmed the two point mutations predicted by the DNA sequence: a glycine-to-glutamate substitution at position 40 and an aspartate-to-asparagine substitution at position 50. Our results further showed that lysine 13 and lysine 115 were methylated normally in cam12. It is likely that the electrophysiological abnormalities of cam12 are a direct reflection of the amino-acid substitutions, as opposed to improper posttranslational modification.


Process engineering of natural killer cell-based immunotherapy.
Cell therapy offers the potential for curative treatment of cancers. Although T cells have been the predominantly used cell type, natural killer (NK) cells have attracted great attention owing to their ability to kill cancer cells and because they are naturally suitable for allogeneic applications. Upon stimulation by cytokines or activation by a target cell, NK cells proliferate and expand their population. These cytotoxic NK cells can be cryopreserved and used as an off-the-shelf medicine. The production process for NK cells thus differs from that of autologous cell therapies. We briefly outline key biological features of NK cells, review the manufacturing technologies for protein biologics, and discuss their adaptation for developing robust NK cell biomanufacturing processes.


Continuous production of cephalosporin-C by immobilized microbial cells using symbiotic mode in a packed bed bioreactor.
Cephalosporins are usually produced semisynthetically from Cephalosporin-C, which is exclusively produced by Cephalosporium acremonium. Free cell studies for the production of Cephalosporin-C had some limitation such as pulpy growth of fungus causing an appreciable rise in the broth viscosity affecting the transfer of oxygen and other nutrients into the cells. High cell concentrations cannot be maintained because of wash out phenomenon at high dilution rates. The whole cell immobilization technique is a potentially important process for Cephalosporin-C biosynthesis, where increase cell densities were maintained and broth-handling problems were reduced. Cephalosporin-C fermentation is a highly aerobic process. The symbiotic relationship of Cephalosporium acremonium and Chlorella pyrenoidosa has been used to increase oxygen transfer rate to the fungi by co-immobilizing it with algae. Co-immobilization of whole cells of fungus and algae were carried out in different immobilizing agents and the systems were coated with polyacrylamide resin of pharmaceutical grade to overcome the problems of leakage. The operational stability of immobilized systems in a packed bed reactor was also studied.


Electron beam radiotherapy for tongue cancer using an intra-oral cone.
To explain the adaptation technique using an intra-oral cone (IOC) for radiation therapy, and to determine the optimal schedule resulting in a high local control rate and an acceptable complication rate using direct electron beam radiation for the treatment of tongue cancer. Thirty patients with the tongue cancer (T1:T2:T3=16:11:3) were treated with 6-15 MeV electron radiation using an IOC. Twenty-six patients were treated with electron radiation using an IOC with or without an excisional biopsy. The other four patients were treated with a combination of the external beam radiation and electron radiation using the IOC. In order to formulate a safe and effective treatment program, we calculated the biologically effective dose (BED). The two- and five-year local control rates for all patients were 63% and 52%, respectively. The two- and five-year overall survival rates for all patients were 73% and 69%, respectively. Local control was achieved in 12 of 15 patients who were irradiated with a BED of 90.9 Gy(10) or more, whereas it was not achieved in nine of the 15 patients who were treated with less than a BED of 90.9 Gy(10) (p=0.03). The application of electron radiation using an IOC for the treatment of tongue cancer provides acceptable local control and adverse effect rates, especially for elderly patients considered to be high risk for complications from anesthesia. The optimum BED(10) value for the treatment of early tongue cancer using the IOC technique appears to be at least 90.9 Gy(10).


Ferric Carboxymaltose Across All Ages in Paediatric Gastroenterology Shows Efficacy Without Increased Safety Concerns.
The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. This was a retrospective study of all gastroenterology patients <18 years who had FCM (October 2015 to October 2017). Haematological and biochemical parameters were recorded pre-infusion, at 4 weeks, 3 months, 6 months, and 1 year post-infusion. Recognised side-effects were documented. Sixty-six children received FCM during this period. Data was analysed on 61 children, 5 excluded because of inadequate data. The median age at administration was 14 years (IQR 7). Thirty-two (52%) were boys. Twenty-six (42%) were <14 years old. Seven (11.5%) were <5 years old. Seventeen (28%) were switched from oral iron supplements to FCM. The median dose of FCM delivered was 19 mg/kg. The median haemoglobin increased from 108 to 126 g/L at 1 month post-infusion (P value <0.00001). The mean cell volume also improved from 80 to 84 fL at 1 month post-infusion (P value = 0.0007). Forty-eight (94%) children corrected their anaemia after receiving FCM. Two patients (3%) reported side-effects with skin bruising and staining. FCM appears to be effective in correcting IDA in children across a wide range of gastroenterology indications and all ages. It is effective and generally well tolerated including in very young patients. Potential side-effects can be avoided by careful monitoring during infusions.


Initiation of early breeding in a population of Microtus townsendii (Rodentia) with the secondary plant compound 6-MBOA.
Feeding the secondary plant compound 6-Methoxybenzoxazolinone (6-MBOA) during winter to a free living population of Microtus townsendii accelerated breeding in females. Both the recruitment of young and sexual maturation of these young were advanced by four weeks in comparison with a control population. Overwintered females supplied with 6-MBOA matured at a lower body weight than control females. But there was no such weightat-maturity difference between the grids for males. During April and May 72% of all juveniles captured came from the experimental population. Winter reproduction and early recruitment of young stimulated by 6-MBOA could have important population consequences for these voles.


[Occupation of health care system because of body complaints by young people--results of a representative survey].
In a sample of adolescents between 14 and 25 years of age (n=266), drawn from a sample of 2089 representatively selected people, we found that a significant part of the adolescents suffers from physical complaints. The regions which were most frequently affected were head or face (33%), back (24%), and stomach (22%). We did not find significant influences of sociodemographic parameters like age, gender and residence on the prevalence of physical complaints in adolescents. Adolescents occupy the health care system frequently because of physical complaints. In comparison to adults, younger people suffer less from physical complaints and occupy the health care system significantly less often. It seems that somatoform complaints begin in young age, but that they do not reach their chronic form until adulthood. Early interventions are necessary to reduce individual suffering and to act in an economically responsible way.


Oncogenes.
Particular eukaryotic genes which play integral roles in the control of normal growth and differentiation programs are targets for mutagenic events which lead to the generation of malignancies. These genes, called proto-oncogenes can be activated to the oncogenic state by amplification, point mutation, deletion or chromosomal translocation. The protein products encoded by oncogenes include protein kinases, G-proteins, growth factors and nuclear transcription factors. It is likely that oncogene activation by viral infection or in concert with virally-induced immunodeficiencies is responsible for the aetiology of human tumours.


Epidemiology and issues of NIV-treated AECOPD patients with hypercapnic respiratory failure in Shanghai: A multicentre retrospective survey.
To investigate the epidemiology, clinical features, treatment and outcome of Noninvasive ventilation (NIV)-treated acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in secondary hospitals of Shanghai. Relying on Shanghai alliances for respiratory diseases, a retrospective observational study was performed in 34 secondary hospitals of Shanghai. The AECOPD patients treated with NIV and admitted to the respiratory department or respiratory intensive care unit were recruited between December 1, 2016, and November 30, 2017. There were 555 patients finally recruited in this study. The age was 75.8 ± 9.6 years old and 380 patients (68.5%) were male. 70.5% of all patients had respiratory acidosis (pH <7.35). 55.3% of all patients received nebulised bronchodilator and 77.7% were treated with systemic or inhaled corticosteroids during hospitalisation. 525 patients (94.6%) recovered successfully and the mortality was 3.2%. The hospitalisation was 15.3 ± 6.7 days and hospital expenses were 22 911 ± 13 595 RMB. Inadequate and nonstandard drug treatments were the most important problems during management. The NIV can be successfully used for AECOP patients in local hospitals of Shanghai, but accompanied by high costs and long hospital stays. However, the treatments for exacerbation and stable COPD patients are still insufficient.