Cisplatin, bleomycin and methotrexate in the treatment of advanced oesophageal cancer.
From February 1981 to September 1982, 34 patients with metastatic or locally advanced (inoperable) epidermoid carcinoma of the oesophagus were treated with a combination of cisplatin, bleomycin and methotrexate. Thirty-one patients are now evaluable for response: 16 of 31 (52%) experienced some improvement, but only eight (26%) obtained major responses (one complete and seven partial). Responses were obtained rapidly within the first two courses. The median duration of responses was 5 months. The median survival from start of therapy was 8 months for responsive and 5 months for non-responsive patients. Gastrointestinal toxicity (cisplatin-related) and mild myelosuppression were the most prominent side-effects. This combination chemotherapy proved to be only of small efficacy in the long-term control of advanced oesophageal cancer. However, because the responses were obtained rapidly, it is conceivable that a similar regimen (with increased dosage of cisplatin) applied before surgery to patients with limited disease could obtain a reduction of the bulky tumour, with a possible increase of the resectability rate and destruction of micrometastases.


Adsorption of malachite green from aqueous solution by using novel chitosan ionic liquid beads.
Chitosan ionic liquid beads were prepared from chitosan and 1-butyl-3-methylimidazolium based ionic liquids to remove Malachite Green (MG) from aqueous solutions. Batch adsorption experiments were carried out as a function of initial pH, adsorbent dosage, agitation time and initial MG concentration. The optimum conditions were obtained at pH 4.0, 0.008g of adsorbent dosage and 20min of agitation time were utilized in the kinetic and isotherm studies. Three kinetic models were applied to analyze the kinetic data and pseudo-second order was found to be the best fitted model with R2>0.999. In order to determine the adsorption capacity, the sorption data were analyzed using the linear form of Langmuir, Freundlich and Temkin equations. The isotherm was best fitted by Langmuir isotherm model. The maximum adsorption capacity (qmax) obtained from Langmuir isotherm for two chitosan beads 1-butyl-3-methylimidazolium acetate A and 1-butyl-3-methylimidazolium B are 8.07mgg-1 and 0.24mgg-1 respectively.


Prevention of the TPA-mediated down-regulation of protein kinase C.
Protein kinase C activity in lymphocytes was down-regulated upon exposure of the cells to 12-0-tetradecanoylphorbol-13 acetate. This down-regulation was prevented by preincubating the cells with sphingosine, a reported protein kinase C inhibitor. Two other protein kinase C inhibitors, palmitoylcarnitine and phloretin, were ineffective in preventing down-regulation by the phorbol ester.


TNF-α gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea.
To assess sleepiness, TNF-α plasma levels, and genomic variance in the TNF-α gene in children with obstructive sleep apnea (OSA). Children being evaluated for OSA (n = 60) and matched control children (n = 80) were assessed with a modified Epworth Sleepiness Scale questionnaire and underwent a blood draw the morning after nocturnal polysomnography. TNF-α plasma concentrations were assayed using ELISA, and genomic DNA was extracted. Genotyping and allelic frequencies were determined for 4 TNF-α single nucleotide polymorphisms using real-time polymerase chain reaction genotyping assays. Morning TNF-α levels and Epworth Sleepiness Scale scores were increased in the presence of OSA, but substantial variability was present. Although TNF-α plasma concentrations were globally increased in OSA, most of the variance was attributable to the presence or absence of TNF-α -308G gene polymorphism. TNF-α levels are increased in a subset of children with OSA, particularly among those harboring the TNF-α -308G single nucleotide polymorphism. Among the latter, significant increases in excessive daytime sleepiness symptoms are also present. The relatively high variability of excessive daytime sleepiness in pediatric OSA may be related to underlying TNF-α gene polymorphisms, particularly -308G.


Surgical management of massive pulmonary embolism.
Between 1972 and 1976, 24 patients have been treated by open pulmonary embolectomy with the aid of cardiopulmonary bypass (CPB). In 17 (71 percent) acute pulmonary embolism occurred 3 to 60 days after a surgical procedure. The remaining seven (29 percent) patients had chronic medical diseases. The interval between clinical manifestation of acute pulmonary embolism and the performance of open embolectomy ranged from 8 to 36 hours. The definitive diagnosis in all patients was made by pulmonary arteriography. Candidates for pulmonary embolectomy were selected by assessment of hemodynamic stuides: shock, arterial Po2 less than 65 mm. Hg, acidosis, pulmonary artery pressure higher than 20 to 30 mm. Hg, and central venous pressure elevated (patients in Class III or IV according to the Greenfield classification). The definitive indication for embolectomy was occlusion of the main pulmonary artery of more than 50 percent as well as occlusion of the right or left pulmonary artery. Of the seven patients operated upon between 1973 and 1974, three (43 percent) died in the early postoperative period. Between 1975 and 1976 the operative mortality rate in 17 patients was 23 percent (four patients). Our results show that prompt diagnosis of acute massive pulmonary embolism and better selection of patients may improve significantly the survival rate after open pulmonary embolectomy with CPB.


Bacteremia caused by Desulfovibrio fairfieldensis.
Desulfovibrio species are anaerobic gram-negative, pleomorphic bacilli rarely causing infection in humans. In the present report, we describe a case of bacteremia caused by Desulfovibrio fairfieldensis. The patient, for whom biapenem was administered, rapidly improved without any sequelae. As far as we know, this is the first case report of infection by Desulfovibrio species in Japan.


What does an elevated troponin mean?--An update on the definition of myocardial infarction.
Myocardial infarction has a high rate of morbidity and mortality. There are major social, psychological and legal implications associated with the diagnosis of myocardial infarction (MI). We present three case studies of different chest pain syndromes presenting with serum troponin elevation, and use these cases to form the basis of a review of the updated definition of MI. A practical approach to the diagnosis of myocardial infarction is also discussed. The measurement of serum troponin levels was a great diagnostic advance and provided powerful prognostic information. Although elevated serum troponin levels were originally considered pathognomonic of MI, it has become clear that highly sensitive troponin assays detected the presence of elevated troponin levels in the absence of MI. This has led to the recent 'Third universal definition of myocardial infarction' consensus document.


[Study of the methods of specific desensitization therapy in immediate hypersensitivity to Streptococcus under experimental conditions. 1. Immunological data].
Three series of experiments were conducted on 427 guinea pigs. A model of allergy of the immediate type was obtained by 3-fold subcutaneous injections of 2 mg of lysed streptoallergen with an imcomplete Freund's adjuvant. The effect of allergens (corpuscular--vaccines, lysed, and streptoallergens after Ando-Verzhikovsky) varying by physico-chemical properties was studied in the first experimental series. The best hyposensitizing action was produced by vaccine used for the study of the influence of various doses on the sensitized organism. Two doses were approved: the threshold one (diluted 10 times) and the subthreshold one (diluted 10000 times). The use of the threshold doses caused reduction of increased sensitivity of the immediate type. In the III experimental series this dose was injected subcutaneously, intradermally, and intravenously. Subcutaneous method proved to produce a more marked hyposensitizing action in comparison with other methods.


Simultaneous preperitoneal hernia repair during radical pelvic surgery.
Hernia repair can be performed safely and expeditiously during radical pelvic surgery using the preperitoneal approach through a median longitudinal incision. We performed 41 preperitoneal herniorrhaphies simultaneously with 343 radical retropubic prostatectomies and 26 radical cystoprostatectomies. There is no evidence of recurrent hernias to date and no complications attributable to the hernia repairs. We present the technique and illustrate the preperitoneal anatomy, which allows the safe, efficacious performance of these procedures.


Influence of age structure of plant populations on damping-off epidemics.
Germination synchrony may facilitate damping-off epidemics by creating a high density of uniformly susceptible individuals. We tested the hypothesis that synchronous germination causes increased seed and seedling mortality from damping-off in two legume species attacked by the fungal pathogen, Pythium aphanidermatum. Glycine max exhibited rapid, synchronous germination compared to its progenitor, G. soja, and suffered greater mortality from both pre-and postemergent damping-off in controlled environment experiments. However, when mixed-aged populations of G. max were created experimentally by staggering planting times, a significant increase in damping-off mortality occurred. In G. soja, which typically has mixed-aged populations due to asynchronous germination, experimental populations with an even-aged distribution also suffered increased damping-off mortality. Hence, the relationship between population age structure and damping-off mortality was species-specific. We propose that species differences in the duration of individual seedling susceptibility to disbase interact with population age structure to control the cutcome of damping-off epidemics.


Resident brain neural precursor cells develop age-dependent loss of therapeutic functions in Alzheimer's mice.
There is vast knowledge on pathogenic mechanisms in Alzheimer's disease but very little on means by which the brain protects itself from disease. A major candidate in providing neuroprotection is the resident brain neural precursor/stem cell (NPC) pool. Transplanted NPCs possess powerful immune-modulatory and trophic properties in vivo and in vitro, underscoring the question whether resident brain NPCs have any role in regulating disease pathology in Alzheimer's disease, and particularly whether they fail to protect the brain from degeneration. To evaluate brain NPC function in relation to disease pathology, we first characterized the pathological properties of 5xFAD transgenic mouse model of Alzheimer's disease at different ages. We found that age 7 months is a critical time point of heavy amyloid deposition and gliosis but before neurodegeneration and a normal basal rate of NPC turnover in the subventricular zone (SVZ) of 5xFAD mice as compared to wild-type mice. Analysis of NPC functional properties showed that despite preserved rate of turnover, there was substantial SVZ NPC dysfunction as indicated by both ex vivo and in vivo assays. Freshly isolated NPCs from 7-month-old 5xFAD mice exhibited reduced expansion rate and diminished immune-modulatory and trophic properties. Moreover, there was slowed recovery of SVZ NPCs after cytosine-arabinoside insult and markedly reduced migratory response following a lysolecithin-induced lesion in the corpus callosum in vivo. Importantly, these functions were fully preserved in 2-month-old 5xFAD mice, a time point before Alzheimer's disease-specific pathological changes. There was reduced expression of key genes involved in NPC proliferative and migratory response in NPCs derived from 7-month-old 5xFAD mice. The dysfunctional properties and downregulation of gene expression were reversible in NPCs derived from 7-month-old 5xFAD mice following in vitro expansion and were reproduced in wild-type NPC by addition of amyloid beta peptide. Thus, there is age-dependent acquired NPC dysfunction, with loss of immune-modulatory and neurotrophic properties, which is induced by the pathological Alzheimer's brain environment at a critical time point before neurodegeneration. We suggest that failure of resident NPC to provide tissue support may be involved in promoting neurodegeneration.


Sustainable risk management practice in the organization: a Malaysian case study.
Businesses are becoming more conscious of operational risk management practices due to the COVID-19 pandemic. However, some firms practice risk management without fully comprehending how it might help them and their needs. As a result, companies that practice risk management without realizing it are being controlled by the discipline itself. The goal of this study is to look into the epistemic process of risk management practice in the workplace. This phenomenological study interviewed 39 risk management officers, executives, and employees. Data are thematically analyzed. This study discovered five epistemic processes of risk mapping using Foucault's governmentality paradigm. This phenomenological study, interestingly, revealed the black box of risk management practices, as well as the behavior of risk management officers, executives, and risk owners who preferred to monitor the compliance aspects of risk management practices rather than comprehend the capabilities of risk management that could be used within their strategic planning process. Unaware of this black box, organizational actors were blanketed by the organization's culture of fear, which created the impression that the authority was always watching every word said and every action taken. Practically, this study contributes an improved understanding of the real function of risk management that helps them justify the practice and reduce unnecessary fear. The paper concludes with limitations and research recommendations.


Nitric oxide enhances thyroid peroxidase activity in primary human thyrocytes.
Recent studies have demonstrated the production of the multi-functional messenger molecule nitric oxide (NO) by the thyroid gland. To examine a possible role for NO in thyroid function, we studied the acute and chronic effect of NO donors on thyroid peroxidase (TPO) activity in monolayer cultures of primary human thyrocytes, using a colorimetric assay technique. The presence of either S-nitrosoglutathione (GS-NO) or sodium nitroprusside (SNP) (10(-6)-10(-4) M) at the time of the assay caused a significant increase in TPO activity. Pre-incubation of thyrocytes with 10(-5) M GS-NO for 3 days had no effect on the level of TPO activity when the assay was performed in the absence of NO donors. However, GS-NO pre-incubation significantly enhanced the acute stimulatory effect of GS-NO and SNP on TPO activity. These results suggest a possible role for NO in the regulation of TPO activity and thus thyroid hormone synthesis.


Sustained negative feedback between haematocrit and serum erythropoietin concentration in end-stage renal failure.
In a longitudinal study the individual values of serum erythropoietin (SEp) in end-stage renal failure were investigated in 15 patients. SEp was determined by use of the foetal mouse liver cell assay on three occasions: (A) 2--6 months before the onset of RDT, (B) on day of first dialysis, and (C) 2--6 months following the onset of RDT. In every patient SEp increased from (A) to (B), and decreased again from (B) to (C). Changes of haematocrit were exactly opposite to changes of SEp. The results demonstrate that even in the terminal stage of chronic renal failure erythropoietin production is stimulated or suppressed in response to variations in the degree of anaemia.


Noninvasive Doppler color flow mapping for detection of anomalous origin of the left coronary artery from the pulmonary artery and for evaluation of surgical repair.
Anomalous origin of the left coronary artery from the pulmonary artery is a rare but important cause of congestive heart failure in infancy and of sudden death at all ages. Diagnosis is often missed when based solely on physical examination and noninvasive methods. A 4 year old patient is presented in whom mitral regurgitation was noted by a referring physician and an anomalous left coronary artery was found by Doppler color flow mapping upon referral and verified at cardiac catheterization. Doppler color flow mapping was also used intraoperatively using a gas-sterilized transducer to further clarify the hemodynamics and assess the surgical result. After creation of an intrapulmonary artery tunnel from the ostium of the left coronary artery to the aorta, anterograde coronary artery flow and absence of a residual left to right pulmonary artery shunt were verified during surgery by Doppler flow mapping. Postoperatively, residual mitral regurgitation and patency of the left coronary artery graft have been followed up serially by Doppler flow mapping. Therefore, Doppler color flow mapping is useful in the diagnosis and intraoperative and postoperative management of this important and potentially life-threatening abnormality.


Differential expression of pattern recognition receptors in the three pathological forms of sheep paratuberculosis.
Paratuberculosis is a chronic inflammatory disease of the gut caused by Mycobacterium avium subspecies paratuberculosis. Three forms have been described in sheep--paucibacillary, multibacillary and asymptomatic. The pauci- and multibacillary forms are characterized by type 1 and type 2 immune responses respectively; asymptomatic animals have no clinical signs or pathology. What determines this polarization is unknown, although pattern recognition receptors (PRR) have been implicated in other mycobacterial diseases. To investigate this in sheep paratuberculosis we used real-time RT-PCR to quantify the expression of fifteen PRR and adaptor genes from forty infected and nine control animals. These data show that there is a relationship between the different pathological forms and PRR transcript profiles. Nine PRRs were up-regulated in asymptomatic animals; with TLR9 being significantly raised in relation to the other three groups. Comparison of the three infected groups showed increases in many PRRs, with CARD15 and Dectin-2 being particularly high in both diseased groups. Significant differences between the pauci- and multibacillary animals included TLR2, CD14 and Dectin-1. Sequence analysis of TLR2 exon 2 and CARD15 exon 11 in the forty animals failed to identify any relationship between SNPs and pathological form.


Quality of life in patients undergoing minimally invasive cardiac surgery: a systematic review.
Minimally invasive procedures have been developed to reduce surgical trauma after cardiac surgery. Clinical recovery is the main focus of most research. Still, patient-centred outcomes, such as the quality of life, can provide a more comprehensive understanding of the impact of the surgery on the patient's life. This systematic review aims to deliver a detailed summary of all available research investigating the quality of recovery, assessed with quality of life instruments, in adults undergoing minimally invasive cardiac surgery. All randomised trials, cohort studies, and cross-sectional studies assessing the quality of recovery in patients undergoing minimally invasive cardiac surgery compared to conventional cardiac surgery within the last 20 years were included, and a summary was prepared. The randomised trial observed an overall improved quality of life after both minimally invasive and conventional surgery. The quality of life improvement in the minimally invasive group showed a faster course and evolved to a higher level than the conventional surgery group. These findings align with the results of prospective cohort studies. In the cross-sectional studies, no significant difference in the quality of life was seen except for one that observed a significantly higher quality of life in the minimally invasive group. This systematic review indicates that patients may benefit from minimally invasive and conventional cardiac surgery, but patients undergoing minimally invasive cardiac surgery may recover sooner and to a greater extent. However, no firm conclusion could be drawn due to the limited available studies. Therefore, randomised controlled trials are needed.


Methoctramine reveals heterogeneity of M2 muscarinic receptors in longitudinal ileal smooth muscle membranes.
Direct binding studies on longitudinal ileal and atrial muscarinic receptors revealed that most of the ileal or atrial selective antagonists identified in functional studies did not differentiate between these muscarinic receptors in direct binding studies. Methoctramine, an atrial selective muscarinic receptor antagonist in functional studies was, however, able to partially discriminate between these two receptors in our binding studies. Furthermore the binding data obtained using this compound indicated that longitudinal ileal muscarinic receptors were heterogeneous. The predominant population of ileal muscarinic receptors displayed a similar pharmacology to the cardiac type M2 muscarinic receptor. The minor population of muscarinic receptors identified in binding studies displayed a similar pharmacology to the ileal muscarinic receptor identified in functional studies and were pharmacologically similar to the exocrine gland type M2 muscarinic receptor.


Coupling efficacy and selectivity of the human mu-opioid receptor expressed as receptor-Galpha fusion proteins in Escherichia coli.
Two constructs encoding the human micro-opioid receptor (hMOR) fused at its C terminus to either one of two Galpha subunits, Galpha(o1) (hMOR-Galpha(o1)) and Galpha(i2) (hMOR-Galpha(i2)), were expressed in Escherichia coli at levels suitable for pharmacological studies (0.4-0.5 pmol/mg). Receptors fused to Galpha(o1) or to Galpha(i2) maintained high-affinity binding of the antagonist diprenorphine. Affinities of the micro-selective agonists morphine, [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), and endomorphins as well as their potencies and intrinsic activities in stimulating guanosine 5'-O-(3-[(35)S]thiotriphosphate) ([(35)S]GTPgammaS) binding were assessed in the presence of added purified Gbetagamma subunits. Both fusion proteins displayed high-affinity agonist binding and agonist-stimulated [(35)S]GTPgammaS binding. In the presence of Gbetagamma dimers, the affinities of DAMGO and endomorphin-1 and -2 were higher at hMOR-Galpha(i2) than at hMOR-Galpha(o1), whereas morphine displayed similar affinities at the two chimeras. Potencies of the four agonists in stimulating [(35)S]GTPgammaS binding at hMOR-Galpha(o1) were similar, whereas at hMOR-Galpha(i2), endomorphin-1 and morphine were more potent than DAMGO and endomorphin-2. The intrinsic activities of the four agonists at the two fusion constructs were similar. The results confirm hMOR coupling to Galpha(o1) and Galpha(i2) and support the hypothesis of the existence of multiple receptor conformational states, depending on the nature of the G protein to which it is coupled.


[Dedifferentiation of chrondrosarcomas (author's transl)].
The clinical course and the results of radiographic and histological investigations in three patients with dedifferentiated chondrosarcoma are presented. The tumors were characterized by chondrosarcomatous tumor sections of low grade malignancy adjacent to fibrosarcomatous tissue sections. One to two and one-half year after the onset of the first clinical symptoms pulmonary metastases appeared and in one case a subcutaneous mass presented, which had the histological appearance of a fibrosarcoma. Differentiation of a chondrosarcoma customarily has an adverse effect on the prognosis with both the early appearance of metastases and a rapidly fatal clinical course. Cartilagenous tumors of the axial skeleton and the long bones must be extirpated surgically in an early and radical fashion, particularly if there are radiographic signs of proliferation.


Distinct serum metabolomic signatures of multiparous and primiparous dairy cows switched from a moderate to high-grain diet during early lactation.
Feeding of high-grain diets is common in cows during early lactation, but increases the odds of metabolic derailments, which can likely be detected as undesirable shifts in the serum metabolome signature. The present study aimed to identify the metabolic signatures of the serum metabolome of early lactation dairy cows switched from a moderate to a high-grain diet. Targeted ESI-LC-MS/MS-based metabolomics was used to characterize metabolic alterations in the serum of early lactation multiparous (MP, n = 16) and primiparous (PP, n = 8) Simmental cows, according to parity and feeding phase. Data were analysed using different data mining approaches. Carnitine, acetylcarnitine, propionoylcarnitine, amino acid related compounds cis-4-hydroxyproline, trans-4-hydroxyproline, proline betaine, lysophosphatidylcholine PC a C16:1 and phosphatidylcholine PC ae C36:0 were identified as the key metabolites distinguishing MP from PP cows. A different serum metabolite composition during moderate and high-grain diet was also evident. Notably, cows fed high grain diet had higher serum concentrations of primary bile acids and triglycerides, but lower levels of conjugated bile acids and carboxylic acids during the first week in grain. Amino acids valine, cystine and taurine together with lysophosphatidylcholine PC a C26:0 and several phosphatidylcholines were classified as important features for cluster separation. Our study greatly expands earlier observations on dietary effects on serum metabolome composition of cows. The altered metabolomic fingerprints clearly distinguishable by diet and cow parity hold potential to be used as early diagnostic tools for cows experiencing grain-induced metabolic disturbances.


Protein methylation in animal cells. II. Inhibition of S-adenosyl-L-methionine:protein(arginine) N-methyltransferase by analogs of S-adenosyl-L-homocysteine.
1. Protein methylase I (S-adenosyl-L-methionine: protein (arginine) N-methyltransferase, EC 184.108.40.206) has recently been purified in our laboratory from Krebs II ascites cells (Casellas, P. and Jeanteur, P. (1978) Biochim. Biophys. Acta 519, 243--254). In order to probe its binding site for S-adenosyl-L-methionine, three series of compounds deriving from the most potent competitive inhibitor, S-adenosyl-L-homocysteine, by specific alterations in each of the three regions of the molecule (amino acid side chain, ribose and adenine) have been tested for inhibitor activity. A competitive type of inhibition was assumed for all of them and demonstrated for five representative ones. The contribution of each of these regions to the binding could therefore be established as follows: (i) Any modification of the side chain results in a drop in affinity of about two orders of magnitude. Adenosine itself remained significantly inhibitory thereby demonstrating that the presence of a side chain was not critical, although important. (ii) The ribose moiety appears to be an essential part of the molecule as the loss of either 2'- or 3'-hydroxyls or their change to arabino configuration resulted in a nearly complete loss of activity. (iii) The amino group at position 6 and the nitrogen atom at position 7 of the adenine ring also play a crucial role although some substitutions can be tolerated. 2. S-Isobutyladenosine was shown to specifically inhibit the methylation of arginine residues as compared to lysine.


Exploring the structure of a neuropsychological battery across healthy elders and those with questionable dementia and Alzheimer's disease.
An exploratory factor analysis (EFA) and a series of confirmatory factor analyses were conducted on 17 variables designed to assess different cognitive abilities in a sample of healthy older adults. In the EFA, 4 factors emerged corresponding to language, memory, processing speed, and fluid ability constructs. The results of the confirmatory factor analyses suggested that a 5-factor model with an additional Attention factor improved the fit. The invariance of the 5-factor model was examined across 3 groups: a group of cognitively healthy older adults, a group of patients diagnosed with questionable dementia (QD), and a group of patients diagnosed with probable Alzheimer's disease (AD). Results of the invariance analysis suggest that the model may have configural invariance across the 3 groups but not metric invariance. Specifically, preliminary analyses suggest that the memory construct may represent something different in the QD and AD groups as compared to the healthy older adult group, consistent with the underlying pathology in early AD.


Quantitative [14C]2-deoxyglucose study of a functional dissociation between anterior and posterior cingulate cortices in mice.
We have previously shown that lesion of the posterior cingulate cortex (CCP) but not of the anterior cingulate cortex (CCA), produced learning and memory deficits. As a first evaluation of the functional anatomical basis of this dissociation, we used the quantitative [14C]2-deoxyglucose method and electrical brain stimulation to determine the functional connections of the CCA and CCP in mice. CCP stimulation (but not CCA stimulation) produced significant metabolic increases in the hippocampal formation and in the subicular complex. This result is consistent with the hypothesis that learning and memory deficits following CCP lesion may be due to the disruption of functional neural pathways between the CCP and hippocampal structures.


Valacyclovir prophylaxis for herpes simplex virus infection or infection recurrence following laser skin resurfacing.
The CO2 laser for cutaneous resurfacing has been associated with the reactivation of herpes simplex virus (HSV), causing delayed reepithelialization and scarring. Antiviral agents appear to be effective in reducing reactivation, however, the optimal therapeutic regimen has yet to be clearly defined. To assess the reactivation rates of HSV after CO2 laser resurfacing in patients who received prophylactic valacyclovir for either 10 or 14 days. One hundred twenty patients received valacyclovir 500 mg twice a day for either 10 or 14 days starting the day prior to facial laser resurfacing. Serology levels and consecutive Tzank preparations were obtained to determine past exposure to HSV and the presence of virus. No patients in either group developed an HSV infection or had a recurrence. These results support the use of valacyclovir in a 10- or 14-day regimen as a preventive agent against HSV outbreaks following facial laser resurfacing.


Comparing knowledge of beta-thalassemia in samples of Italians, Italian-Americans, and non-Italian-Americans.
The purpose of this study was to determine the level of beta-thalassemia awareness among Italians living on the eastern side of Sicily (Bronte, Catania, and Tortorici, Messina), Italian-Americans, and Americans of other ethnic backgrounds (Other-Americans). A questionnaire was developed which asked respondents knowledge questions about both beta-thalassemia and Down Syndrome. Five hundred questionnaires were distributed, and 456 were ultimately returned and analyzed (150 Italians, 156 Italian-Americans, 150 Other-Americans). Italians answered an average of 55% of the beta-thalassemia correctly compared to scores of 17 and 24% for the Italian-Americans and Other-Americans, respectively. The groups did not differ in their knowledge of Down Syndrome (all answered between 58 and 60% of the questions correctly on average). Over 80% of the Italian respondents had heard of beta-thalassemia compared to only 19% of the Italian-Americans. beta-Thalassemia education programs in Italy appear to have dramatically increased awareness of the disorder. Similar programs need to be developed for at-risk populations in the United States.


Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.
We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.


Charge transfer enhanced annihilation leading to deterministic single photon emission in rigid perylene end-capped polyphenylenes.
Two new peryleneimide end-capped polyphenylenes are shown to be deterministic single photon sources in PMMA films due to efficient annihilation between charge transfer states.


Evaluation of current practices in surgical antimicrobial prophylaxis in primary total hip prosthesis--a multicentre survey in private and public French hospitals.
Deep wound infection is a rare but dreaded postoperative complication after total hip prosthesis (THP) procedures but its incidence can be reduced by systemic antimicrobial prophylaxis. The objective of the present study was to evaluate whether antimicrobial prophylaxis for elective primary THP in patients without any history of hip infection, in orthopaedic wards, participating on a voluntary basis, in French public hospitals and private institutions, complies with published guidelines. Three types of data were collected from anaesthetic and surgical records (November 2000-January 2001) in participating hospitals: (1) administrative data on the hospitals and orthopaedic wards, (2) data on patients, (3) data on compliance of practices with five critical criteria derived from published French guidelines. These criteria concerned administration of prophylaxis, choice of antimicrobial agent, dose of first injection, timing of administration and total length of prophylaxis. Thirty institutions sent data files on 1257 THPs to the coordination centre. Compliance exceeded 80% for all criteria except one (interval between first and second injection). Cumulative compliance with the five criteria was 66.9%. Major compliance failures were an inappropriate interval between the first injection and incision, and total antimicrobial prophylaxis exceeding 48 h. Cumulative compliance was 87.9% in teaching hospitals, 61.8% in general hospitals and 67.7% in private institutions (P<1 x 10(-6)). It was slightly higher when the annual number of interventions was > or =100 (69.4 versus 62.3%; P<0.02). Although the protocol for antimicrobial prophylaxis in THP was clear and easy, one-third of practices did not conform with all five standards. Knowledge of the results by the participating institutions should encourage them to set up working groups to draft care protocols for THP and other surgical interventions, in order to improve practice and perhaps reduce costs.


Ultrastructural protein zero expression in Charcot-Marie-Tooth type 1B disease.
Charcot-Marie-Tooth type 1B (CMT 1B) disease, an inherited demyelinating peripheral neuropathy, results from different point mutations located in the P0 gene on chromosome 1 q21-23. We have quantified, at the ultrastructural level, the immunocytochemical expression of the P0 protein in two unrelated CMT 1B patients with mutations (Ser 78 to Leu and Asn 122 to Ser) located in two different exons in the extracellular domain of the protein. A twofold decrease in P0 expression was observed in compact myelin in each case, compared with age-matched controls. The severity of the phenotypes showed no direct relationship to the levels of P0 protein expression in these 2 patients.


Effects of immobility on sensory and motor symptoms of restless legs syndrome.
Restless legs syndrome (RLS) is defined by an irresistible need to move associated with leg paresthesia. Two additional features are essential for diagnosis: (1) worsening of symptoms at rest with temporary relief by activity, and (2) worsening of symptoms during the evening and/or during the night. The suggested immobilization test (SIT) has been developed to evaluate the presence of these criteria. This test quantifies leg movements and leg discomfort during a 1-hour period of immobility prior to bedtime. We used the SIT to evaluate the effects of immobility on leg discomfort and leg movements experienced by 19 patients with RLS and 19 control subjects. Results show that immobility significantly worsens both leg discomfort and periodic leg movements (PLM) in patients with RLS but not in controls. Patients with RLS showed a higher leg discomfort score (32.6 +/- 15.1 mm vs. 5.7 +/- 7.9 mm; P < 0.00001), a greater maximum leg discomfort value (63.4 +/- 27.4 mm vs. 13.7 +/- 23.0 mm; P < 0.00001) and a greater PLM index (88.4 +/- 62.6 vs. 10.4 +/- 20.6; P < 0.00004) than control subjects. These results further validate the use of the SIT as a diagnostic and research tool for RLS and confirm the contention of the International RLS study group that RLS symptoms worsen at rest.


Trends in US hospitalizations for anaphylaxis among infants and toddlers: 2006 to 2015.
Anaphylaxis is a potentially fatal acute allergic reaction. Its overall prevalence appears to be rising, but little is known about US hospitalization trends among infants and toddlers. To identify the trends and predictors of hospitalization for anaphylaxis among infants and toddlers. We used the nationally representative National Inpatient Sample (NIS), from 2006 to 2015, to perform an analysis of trends in US hospitalizations for anaphylaxis among infants and toddlers (age, <3 years) and other children (age, 3-18 years). For internal consistency, we identified patients with anaphylaxis by the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code and excluded those with the International Classification of Diseases, Tenth Revision, Clinical Modification (late 2015). We calculated trends in anaphylaxis hospitalizations over time by age group and then used multivariable logistic regression to describe anaphylaxis hospitalizations among infants and toddlers. Among infants and toddlers, there was no significant change in anaphylaxis hospitalizations during the 10-year study period (Ptrend = .14). Anaphylaxis hospitalization among infants and toddlers was more likely in males, with private insurance, in the highest income quartile, with chronic pulmonary disease, who presented on a weekend day, to an urban teaching hospital, located in the Northeast. In contrast, anaphylaxis hospitalizations among older children (age, 3-<18 years) rose significantly during the study (Ptrend < .001). Anaphylaxis hospitalizations among infants and toddlers in the United States were stable from 2006 to 2015, whereas hospitalizations among older children were rising. Future research should focus on the trends in disease prevalence and health care utilization in the understudied population of infants and toddlers.


Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric aciduria.
L-2-Hydroxyglutaric aciduria is a rare inborn error of metabolism, marked by a large and persistent increase of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). We present clinical, biochemical and neuroradiological findings of seven Italian patients aged 4-19 years presenting at different stages of the disease. The disorder was characterized by a progressive neurological syndrome with cerebellar and pyramidal signs, mental deterioration, epilepsy and subcortical leukoencephalopathy on magnetic resonance imaging (MRI). We observed a good correlation between the severity of the disease and the extent of lesions on MRI. We report the result of the first positive prenatal diagnosis.


Initial performance, learning and observer variability for hyperacuity tasks.
Psychophysically-experienced and -inexperienced human observers were tested on 34 different non-stereo and 49 stereo hyperacuity stimuli. Performance reached hyperacuity levels within the first five trials for the non-stereo stimuli. For stereoacuity tasks the results were very different. Even extremely experienced observers with very low thresholds for certain stereo tasks required considerable practice to achieve their best performance for slightly different stereo tasks. Performance on both types of tasks showed considerable observer variability. These results suggest that adults do not synthesize new visual modules for hyperacuity tasks early in the visual pathway on a task-driven basis. We also interpret these results to suggest that there can be many equally general models of hyperacuity performance that show only the qualitative general trends of a "standard" observer. Incorporating individual variability might provide sufficient constraints on such models to provide clues about physiological mechanisms.


Effects of Iraq/Afghanistan deployments on major depression and substance use disorder: analysis of active duty personnel in the US military.
Our objective was to analyze the association between deployment characteristics and diagnostic rates for major depression and substance use disorder among active duty personnel. Using active duty personnel serving between 2001 and 2006 (n = 678,382) and deployment information from the Contingent Tracking System, we identified individuals diagnosed with substance use disorders and major depression from TRICARE health records. We performed logistic regression analysis to assess the effect of deployment location and length on these diagnostic rates. Increased odds of diagnosis with both conditions were associated with deployment to Iraq or Afghanistan compared with nondeployed personnel and with Army and Marine Corps personnel compared with Navy and Air Force personnel. Increases in the likelihood of either diagnosis with deployment length were only observed among Army personnel. There were increased substance use disorders and major depression across services associated with combat conditions. It would be important to assess whether the public health system has adequate resources to handle the increasing need of mental health services in this population.


Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis.
Evodiamine (EVO) was tested on acute gouty arthritis rats to investigate its anti-inflammatory effect. Seventy-two male Sprague-Dawley (SD) rats were randomly assigned into the control, model, high, medium, and low dose of EVO groups and colchicine group. The ankle swelling degrees were measured at 2 h, 6 h, and 24 h following sodium urate injection into ankle joint. Histopathological examination was performed 24 h after injection. Reactive oxygen species (ROS) content in the ankle joint was detected using chemical fluorescence. Serum interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) content were determined by ELISA. Serum xanthine oxidase (XOD), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by spectrophotometry. The expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), pro-caspase-1, caspase-1, and apoptosis-related spot like protein (ASC) in synovium were detected by Western blot. Evodiamine alleviated the ankle swelling of the affected foot in gouty arthritis rats and reduced inflammatory cell infiltration in joint synovial tissue. Evodiamine also decreased the content of serum inflammatory factors including IL-1β, IL-18, and TNF-α, and increased serum SOD activity, while it decreased serum XOD, MDA activity, and ROS level. Moreover, evodiamine downregulated the protein expression levels of TXNIP, NLRP3, pro-caspase-1, cleaved caspae-1, and ASC. The mechanism of EVO in treating gouty arthritis is associated with the inhibition of NLRP3 inflammasome by regulating the ROS/TXNIP/NLRP3 signaling pathway.


Chemistry of Tetradentate [C,N : C,N] Iminophosphorane Palladacycles: Preparation, Reactivity and Theoretical Calculations.
A theoretical and experimental study of tetradentate [C,N : C,N] iminophosphorane palladacycles was carried out for the purpose of elucidating their behavior as compared to the parent Schiff base analogues to determine the prospect of encountering new A-frame structures for the iminophosphorane derivatives. The DFT calculations were in agreement with the experimental results regarding the performance of these ligands. New insights into the chemistry of the related dinuclear species have been obtained.


Blockchain-based medical health record access control scheme with efficient protection mechanism and patient control.
The patient's medical health record (PMHR) has always provided a large amount of research data to medical institutions and pharmaceutical companies, etc., and has contributed to the development in medical research. However, such PMHR data contains the patient's personal privacy and should be shared under the control of the patients, not the hospital where this data is acquired. In order to protect the privacy of PMHR data while realizing efficient data sharing, this paper proposes a blockchain-based sharing and protection scheme. In this solution, the PMHR data are encrypted and stored in a cloud server, which is equipped with an access control scheme implemented as a smart contract on a blockchain. Different from previous works, in order to ensure efficient access and reduce the workload of patients, the types of users who can apply for access are limited to hospitals and pharmaceutical companies. In order to resist the potential Man-in-the-middle (MITM) attack, we have introduced an improved proxy re-encryption scheme to ensure the secrecy of PMHR data while reducing the computational complexity. The whole system is implemented using Solidity and tested on 10 nodes for function verification. Experimental result shows that the proposed system is more efficient than previous systems. Security under the MITM attack is also ensured by security analysis.


Cardiac myocytes activated by septic plasma promote neutrophil transendothelial migration: role of platelet-activating factor and the chemokines LIX and KC.
Cardiac myocytes isolated from rats with peritonitis (cecal ligation and perforation; CLP) promote PMN transendothelial migration. Herein, we assessed (1) the mechanisms involved in cardiac myocyte activation during peritonitis and (2) the means by which these activated myocytes promote PMN transendothelial migration. Plasma obtained from mice subjected to CLP (septic plasma) activated isolated cardiac myocytes as evidenced by (1) increased nuclear levels of nuclear factor-kappaB (NF-kappaB) and (2) their ability to promote PMN migration across endothelial cell monolayers. Pretreatment of septic plasma with an antibody against tumor necrosis factor-alpha (TNF-alpha), but not interleukin-1beta (IL-1beta), blunted the ability of septic plasma to activate the myocytes. However, septic plasma obtained from TNF-alpha-deficient mice could still activate the myocytes; an effect attenuated by an antibody against IL-1beta. If the myocytes were pretreated with a proteasome inhibitor (MG 132) to prevent NF-kappaB activation, the myocyte-induced PMN transendothelial migration was compromised. The activated myocytes released platelet-activating factor (PAF), and myocyte-induced PMN migration was abrogated by a PAF receptor antagonist (WEB 2086). These myocytes also released the CXC chemokines LIX and KC; an event prevented by MG 132. Antibodies against LIX and KC abrogated the myocyte-induced PMN migration. However, LIX and KC, but not PAF, could promote PMN migration when used at concentrations produced by activated myocytes. These observations indicate that TNF-alpha and IL-1beta are, in part, responsible for the ability of septic plasma to activate cardiac myocytes. The activated myocytes promote PMN transendothelial migration, an effect attributable to LIX and KC, and possibly, PAF.


Purification and characterization of human erythrocyte pyridoxine kinase.
A 6000-fold purification of pyridoxine kinase from human erythrocytes has been achieved by a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration and preparative disc polyacrylamide gel electrophoresis. Analytic disc polyacrylamide gel electrophoresis at pH 8.7 reveals two protein bands with similar mobility in the purified enzyme, but only one of these has catalytic activity. The enzyme is found to have a pI of 5.5 and a molecular weight of 65000 by gel filtration, and a broad pH optimum of 8.5. The enzyme is labile at acidic pH. The order of activation of divalent metal ions on the enzyme is Co-2+ greater than Mn-2+ greater than Mg-2+ greater than Zn-2+ greater than Cu-2+ greater than Ni-2+ greater than Fe-2+. Of the monovalent cations studied, K+ is the most effective activator, NH+4 is slightly less effective while Na+ is inhibitory. ATP is the specific phosphate donor for the enzyme. Sulfhydryl reagents did not significantly inhibit the enzyme. The Km for pyridoxine is 5.7 with 10-minus 6 M. Pyridoxal, pyridoxamine and 4-deoxypyridoxine inhibit pyridoxine kinase. Inhibition by pyridoxal is competitive and pyridoxal is observed to be phosphorylated effectively by the enzyme. Young human red cells have a higher activity of pyridoxine kinase than old red cells.


Effects of tumor type on outcomes in patients with large vessel occlusion stroke and cancer.
Large vessel occlusions (LVO) stroke is associated with cancer. Whether this association differs among patients with LVO that undergo endovascular thrombectomy (EVT) according to cancer type remains unknown. Data from consecutive patients that underwent EVT for LVO at three academic centers were pulled and analyzed retrospectively. Patients with LVO and solid tumors were compared to those with hematological tumors. Associations of cancer type with 90-day functional outcome and mortality were calculated in multivariable analyses. Of the 154 patients with cancer and LVO that underwent EVT (mean age 74±11, 43% men, median NIHSS 15), 137 had solid tumors (89%) and 17 (11%) had hematologic tumors. Patients with solid cancer did not significantly differ from those with hematological malignancy in demographics, risk factor profile, stroke severity and subtype, and procedural variables. Outcome parameters including rates of favorable target recanalization and favorable outcome or mortality at discharge and 90 days post stroke were similar. Safety parameters including rates of symptomatic intracranial hemorrhage also did not differ between the groups. On regression analyses, controlling for various prognostic variables cancer type was not associated with mortality or favorable outcomes. Our study suggests that the safety and efficacy of EVT in patients with malignancy does not depend on cancer type. Patients with malignancy should be considered for EVT regardless of cancer type.


Role of the aryl hydrocarbon receptor in tobacco smoke extract-induced matrix metalloproteinase-1 expression.
Findings from large epidemiologic studies indicate that there is a link between smoking and extrinsic skin ageing. We previously reported that matrix metalloproteinases (MMPs) mediate connective tissue damage in skin exposed to tobacco smoke extracts. Tobacco smoke contains more than 3800 constituents, including numerous water-insoluble polycyclic aromatic hydrocarbons (PAHs) that trigger aryl hydrocarbon receptor (AhR) signalling pathways. To analyse the molecular mechanisms involved in tobacco smoke-induced skin ageing, we exposed primary human fibroblasts and keratinocytes to tobacco smoke extracts. Hexane- and water-soluble tobacco smoke extracts significantly induced MMP-1 mRNA in both human cultured fibroblasts and keratinocytes in a dose-dependent manner. To clarify the involvement of the AhR pathway, we used a stable AhR-knockdown HaCaT cell line. AhR knockdown abolished the increased transcription of the AhR-dependent genes CYP1A1/CYP1B1 and MMP-1 induced by either of the tobacco smoke extracts. Furthermore, the tobacco smoke extracts induced 7-ethoxyresorufin-O-deethylase activity, which was almost completely abolished by AhR knockdown. Likewise, treating fibroblasts with AhR pathway inhibitors, that is, the flavonoids 3-methoxy-4-nitroflavone and α-naphthoflavone, blocked the expression of CYP1B1 and MMP-1. These findings suggest that the tobacco smoke extracts induce MMP-1 expression in human fibroblasts and keratinocytes via activation of the AhR pathway. Thus, the AhR pathway may be pathogenetically involved in extrinsic skin ageing.


Magnetic resonance imaging findings of an intracranial medulloblastoma in a Polish Lowland Sheepdog.
Medullobastoma is an uncommon caudal fossa tumor. The imaging features of medullobastoma in the dog are poorly described. In this report, the magnetic resonance (MR) appearance of a cerebellar medullobastoma in a dog is described. The MR features were similar to medulloblastomas in adult humans, with the tumor arising laterally and extending to the surface of the cerebellar hemisphere. Correct localization of medulloblastoma may be difficult and it should be considered as a differential for both extra- and intra-axial caudal fossa masses.


Frequency and reason for reoperation following non-invasive expandable endoprostheses: A systematic review.
Non-invasive expandable endoprostheses (NIEPR) utilize an external electromagnetic field to drive an innate mechanical gearbox. This lengthens the extremity following oncological resections in children with a predicted limb length discrepancy (LLD), facilitating limb-salvage. This review was conducted to assess NIEPR implant survival rates and identify modes of implant failure unique to these prostheses. Medline, EMBASE and the Cochrane Library databases were searched for all manuscripts evaluating implant survival of NIEPRs implanted into skeletally immature patients following resection of extremity sarcomas. Minimum follow-up of 12 months or implant failure was required for inclusion. Failures were classified using the latest ISOLS classification and exact implant-specific failure modality was also identified. 19 studies met inclusion criteria. Mean age was 10.0 years (7.7 - 11.4 years). The most common locations for NIEPR implantation were the distal femur (343, 76.7%) and proximal tibia (53, 119%). Mean follow-up was 65.3 months (19.4 - 163 months). The overall implant revision rate was 46.2% (0 - 100%); implant specific revisions included maximal prosthesis lengthening with persistent LLD (10.4%), failed extension mechanism (6.1%), implant fracture (7.7%), hinge fracture (1.4%) and bushing wear (0.9%). Persistent clinically significant (>20 mm) LLD at final follow-up was present in 19.2% (0 - 50%) of patients. The mean MSTS score was 85.1% (66.7-96.3%) at final follow-up. Implant-related failures are the most common reason for NIEPR revision. Implant reliability appears to be improved with current designs. A sub-classification to the current classification system based on implant-specific failures for NIEPRs is proposed.


Wound complications in obese women after cesarean: a comparison of staples versus subcuticular suture.
To compare wound complications between staples versus subcuticular suture for skin closure in obese women (body mass index (BMI)⩾30 kg m(-2)) after cesarean delivery (CD). We conducted a retrospective cohort study to compare wound complications between staples and subcuticular suture closure in women, with a prepregnancy BMI⩾30 kg m(-2) after CD between 2006 and 2011 at an inner-city teaching hospital. Wound complication was defined as a composite of wound disruption (hematoma or seroma) or infection diagnosed up to 6 weeks postpartum. Variables collected include age, parity, prior CDs, prior abdominal surgeries, incision type, chorioamnionitis, maternal comorbidities (hypertension, diabetes) and gestational age. Of the 1147 women included in the study, women with staple closure were older and had higher BMIs (40.6±9.3 versus 36.1±5.4) and were more likely to be multiparous, have a prior CD, diabetes and hypertension compared with women with subcuticular suture. The overall occurrence of wound complications was 15.5% (178/1147). Women with staples had higher wound complications compared with sutures (22.0% versus 9.7%) with a 2.27 unadjusted relative risk (RR) (95% confidence interval (CI), 1.7 to 3.0) and 1.78 adjusted RR (95% CI, 1.27 to 2.49) after controlling for confounders in the final analysis, including vertical skin incisions. In obese women, skin closure with staples at the time of CD is associated with a higher rate of wound complications compared with subcuticular suture. Skin closure with subcuticular suture over staples should be considered in obese women undergoing a CD regardless of skin incision type.


52 additional reference population samples for the 55 AISNP panel.
Ancestry inference for a person using a panel of SNPs depends on the variation of frequencies of those SNPs around the world and the amount of reference data available for calculation/comparison. The Kidd Lab panel of 55 AISNPs has been incorporated in commercial kits by both Life Technologies and Illumina for massively parallel sequencing. Therefore, a larger set of reference populations will be useful for researchers using those kits. We have added reference population allele frequencies for 52 population samples to the 73 previously entered so that there are now allele frequencies publicly available in ALFRED and FROG-kb for a total of 125 population samples.


Highly diastereoselective type-I IMDA reaction forming medium-sized macrolactones.
[Structure: see text] Intramolecular Diels-Alder (IMDA) reactions of 2-pyrones containing an alkyne tether occur with remarkably high diastereofacial selectivity to provide medium-sized macrolactones. Because of the strain in the alkyne-tethered macrocyclic system, a single methyl group in the tether provides sufficient conformational bias to generate medium-sized macrocycles with unusually high selectivity.


Bioinspired sensor chip for detection of miRNA-21 based on photonic crystals assisted cyclic enzymatic amplification method.
Cancer, as the most invasive disease in the world, has led to an increasing amount of death year by year, so it is highly desired to develop a portable device to monitor the aberrant expression of biomarker in cancer patient. Here, we present a bio-photonic periodic nanostructures sensor chip assisted cyclic enzymatic amplification method to detect miRNA-21 with a detection limit of 55 fM. By employing biocompatible polydopamine nanospheres (PDANs) and DNaseⅠto construct an target-recycling amplification process on the photonic crystals, the output fluorescence signal can be strengthened selectively and short amplification time is needed. Benefiting from the synergy of the enhancement of photonic crystals and enzymatic cycle amplification, we realize high sensitivity detection of miRNA-21 with a detection range of 1 pM-10 nM and a detection limit of about four orders of magnitudes lower than the method employs no amplification, showing an expectable prospect in the early diagnosis of cancer.


Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy.
The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-β (TGF-β) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-β inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs.


Assessing bone quality through mechanical properties in postmenopausal trabecular bone.
The inner structure of trabecular bone is a result of structural optimization provided by remodeling processes. Changes in hormonal status related to menopause cause bone tissue loss and micro-architectural deterioration with a consequent susceptibility to fracture. Accumulation of micro-damage in bone, as a function of the rate of production and rate of repair, underlies the development of stress fractures, increasing fragility associated to age and osteoporosis, especially in transmenopausal women. Quasi-static and nano-dynamic mechanical characterization were undertaken in trabecular bone from femoral neck biopsies of postmenopausal women. AFM (Atomic Force Microscopy) complementary studies were performed to determine nano-roughness (SRa) and the fibrils width of collagen. Nanoindentations were used to quantify transmenopausal changes in intrinsic mechanical properties of trabecular bone: hardness (Hi), modulus of Young (Ei), complex modulus (E*), tan delta (δ), storage modulus (E') and loss modulus (E"). As result of the quasi-static measurements, 0.149 (0.036) GPa and 2.95 (0.73) GPa of Hi and Ei were obtained, respectively. As result of the nano-dynamic measurements, 17.94 (3.15), 0.62 (0.10), 13.79 (3.21 and 6.39 (1.28) GPa of E*, tan (δ), E' and E" were achieved, respectively. 101.07 SRa and 831.28 nm of fibrils width were additionally obtained. This study poses a first approach to the measurement of bone quality in postmenopausal trabecular bone by combining quasi-static, nano-DMA analysis and tribology of dentin surface through AFM characterization.


Bifunctional aryliodonium salts for highly efficient radioiodination and astatination of antibodies.
In this report we describe the development of an alternative approach to arylstannane chemistry for radiolabeling antibodies with radioiodine or astatine based on aryliodonium salts precursors. Bifunctional aryliodonium salts were designed and tested for the synthesis of 125I and 211At labeled prosthetic groups for bioconjugation. The nature of the electron rich aryl group was varied and its impact on the regioselectivity of radiohalogenation was evaluated. Unexpectedly, whereas the 2-thienyl group provided the best regioselectivity towards the radioiodination of the aryl moiety of interest (98:2), it was less selective for astatination (87:13); the anisyl group providing the best regioselectivity of astatination (94:6). Under optimized conditions, both radioiodination and astatination could be performed very efficiently in mild conditions (radiochemical yields>85%). The ionic nature of the precursors was exploited to develop an efficient purification approach: the HPLC step that is usually necessary in conventionnal approaches to optimize removal of organotin toxic precursors and side products was replaced by a filtration through a silica cartridge with a significantly reduced loss of radiolabeled product. The purified radioiodinated and astatinated prosthetic groups were then conjugated efficiently to an anti-CD138 monoclonal antibody (75-80% conjugation yield). By using this novel and simple radiohalogenation procedure, higher overall radiochemical yields of astatination were obtained in comparison with the use of an arylstannane precursor and procedures of the litterature for labeling the same antibody. Overall, due to their simplicity of use and high robustness, these new precursors should simplify the labeling of proteins of interest with iodine and astatine radioisotopes for imaging and therapeutic applications.


Primary Musculoskeletal Lymphoma.
Primary lymphoma of bone and soft tissue is rare and almost invariably of B-cell origin. Osseous lymphoma usually reveals aggressive bone destruction and associated soft tissue extension. Soft tissue involvement is optimally depicted by MR imaging. Cortical destruction allowing communication between the intraosseous and soft tissue components may be subtle with small striations of extension. Lymphoma of the deep soft tissues usually reveals long cones of intramuscular or intermuscular tumor again best depicted by MR imaging. Cutaneous or subcutaneous lymphoma demonstrates multiple nodules and plaquelike thickening.


A novel method for measuring human lipoprotein lipase and hepatic lipase activities in postheparin plasma.
The objective of this study was to establish a new lipoprotein lipase (LPL) and hepatic lipase (HL) activity assay method. Seventy normal volunteers were recruited. Lipase activities were assayed by measuring the increase in absorbance at 546 nm due to the quinoneine dye. Reaction mixture-1 (R-1) contained dioleoylglycerol solubilized with lauryldimethylaminobetaine, monoacylglycerol-specific lipase, glycerolkinase, glycerol-3-phosphate oxidase, peroxidase, ascorbic acid oxidase, and apolipoprotein C-II (apoC-II). R-2 contained Tris-HCl (pH 8.7) and 4-aminoantipyrine. Automated assay of lipase activities was performed with an automatic clinical analyzer. In the assay for HL + LPL activity, 160 microl R-1 was incubated at 37 degrees C with 2 microl of sample for 5 min, and 80 microl R-2 was added. HL activities were measured under the same conditions without apoC-II. HL and LPL activities were also measured by the conventional isotope method and for HL mass by ELISA. Lipase activity detected in a 1.6 M NaCl-eluted fraction from a heparin-Sepharose column was enhanced by adding purified apoC-II in a dose-dependent manner, whereas that eluted by 0.8 M NaCl was not. Postheparin plasma-LPL and HL activities measured in the present automated method had high correlations with those measured by conventional activity and mass methods. This automated assay method for LPL and HL activities is simple and reliable and can be applied to an automatic clinical analyzer.


Complex genome evolution in Anopheles coluzzii associated with increased insecticide usage in Mali.
In certain cases, a species may have access to important genetic variation present in a related species via adaptive introgression. These novel alleles may interact with their new genetic background, resulting in unexpected phenotypes. In this study, we describe a selective sweep on standing variation on the X chromosome in the mosquito Anopheles coluzzii, a principal malaria vector in West Africa. This event may have been influenced by the recent adaptive introgression of the insecticide resistance gene known as kdr from the sister species Anopheles gambiae. Individuals carrying both kdr and a nearly fixed X-linked haplotype, encompassing at least four genes including the P450 gene CYP9K1 and the cuticular protein CPR125, have rapidly increased in relative frequency. In parallel, a reproductively isolated insecticide-susceptible A. gambiae population (Bamako form) has been driven to local extinction, likely due to strong selection from increased insecticide-treated bed net usage.


The role of quantum mechanics in cognition-based evolution.
In 2021 I noted that in all information-based systems we understand, Cognition creates Code, which controls Chemical reactions. Known agents write software which controls hardware, and not the other way around. I proposed the same is true in all of biology. Though the textbook description of cause and effect in biology proposes the reverse, that Chemical reactions produce Code from which Cognition emerges, there are no examples in the literature demonstrating either step. A mathematical proof for the first step, cognition generating code, is based on Turing's halting problem. The second step, code controlling chemical reactions, is the role of the genetic code. Thus a central question in biology: What is the nature and source of cognition? In this paper I propose a relationship between biology and Quantum Mechanics (QM), hypothesizing that the same principle that enables an observer to collapse a wave function also grants biology its agency: the organism's ability to act on the world instead of merely being a passive recipient. Just as all living cells are cognitive (Shapiro 2021, 2007; McClintock 1984; Lyon 2015; Levin 2019; Pascal and Pross, 2022), I propose humans are quantum observers because we are made of cells and all cells are observers. This supports the century-old view that in QM, the observer does not merely record the event but plays a fundamental role in its outcome.The classical world is driven by laws, which are deductive; the quantum world is driven by choices, which are inductive. When the two are combined, they form the master feedback loop of perception and action for all biology. In this paper I apply basic definitions of induction, deduction and computation to known properties of QM to show that the organism altering itself (and its environment) is a whole shaping its parts. It is not merely parts comprising a whole. I propose that an observer collapsing the wave function is the physical mechanism for producing negentropy. The way forward in solving the information problem in biology is understanding the relationship between cognition and QM.


Retracted: A Corpus-Driven Study on Three Elements of Third Personal Pronoun Endophora in English Abstracts of Chinese and Foreign Theses.
[This retracts the article DOI: 10.1155/2022/5981285.].


Posterior short segment fixation including the fractured vertebra combined with kyphoplasty for unstable thoracolumbar osteoporotic burst fracture.
Various studies have described the efficacy and safety of the treatment for unstable thoracolumbar osteoporotic burst fracture, however, there is still no consensus on the optimal treatment regimen. The aim of this study was to evaluate the clinical and radiographic results of posterior short segment fixation including the fractured vertebra (PSFFV) combined with kyphoplasty (KP) for unstable thoracolumbar osteoporotic burst fracture. Forty-three patients with unstable thoracolumbar osteoporotic burst fracture underwent PSFFV combined with KP from January 2015 to December 2017 were analyzed retrospectively. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was used to evaluate the clinical outcome, radiological parametres including local kyphotic Cobb angle, percentage of the anterior, middle and posterior height of the fractured vertebra were measured and compared pre-operation, post-operation and at final follow-up. All patients underwent surgery successfully and with an average follow-up of 19.2 ± 6.7 months (rang 15-32). The VAS decreased from 7.1 ± 2.3 pre-operation to 1.6 ± 0.4 at the final follow-up (p < 0.05). The ODI decreased from 83.1 ± 10.5 pre-operation to 19.2 ± 7.3 (P < 0.05) at the final follow-up. The correction of local kyphotic angle was 16.9° ± 5.3° (p < 0.05), and the loss of correction was 3.3° ± 2.6° (p > 0.05), the correction of anterior vertebral height was 30.8% ± 8.6% (p < 0.05), and the loss of correction was 4.5% ± 3.9% (p > 0.05), the correction of middle vertebral height was 26.4% ± 5.8% (p < 0.05), and the loss of correction was 2.0% ± 1.6% (p > 0.05), the correction of posterior vertebral height was 9.4% ± 6.9% (p < 0.05), and the loss of correction was 1.6% ± 1.3% (p > 0.05). Two cases of screw pullout and 8 cases of cement leakage were observed, but without clinical consequence. PSFFV combined with KP is a reliable and safe procedure with satisfactory clinical and radiological results for the treatment of unstable thoracolumbar osteoporotic burst fracture.


Photobiomodulation and vitamin B treatment alleviate both thermal and mechanical orofacial pain in rats.
The present study investigates the efficacy of Photobiomodulation (PBM) and Vitamin B Complex (VBC) to relieve pain, both in separately and combined (PBM and VBC). Rats with chronic constriction injury of the right infraorbital nerve (CCI-IoN) or Sham surgery were used. PBM was administered at a wavelength of 904 nm and energy density of 6.23 J/cm2 and VBC (containing B1, B6 and B12) subcutaneously, both separately and combined. Behavioral tests were performed to assess mechanical and thermal hypersensitivity before and after CCI and after PBM, VBC, or PBM + VBC. The expression of inflammatory proteins in the trigeminal ganglion and the immunohistochemical alterations of Periaqueductal Gray (PAG) astrocytes and microglia were examined following CCI and treatments. All testeds treatments reversed the painful behavior. The decrease in pain was accompanied by a decrease of Glial Fibrillary Acidic Protein (GFAP), a specific astrocytic marker, and Ionized calcium-binding adaptor molecule 1 (Iba-1), a marker of microglia, and decreased expression of Transient Receptor Potential Vanilloid 1 (TRPV1), Substance P, and Calcitonin Gene-Related Peptide (CGRP) induced by CCI-IoN in PAG and Trigeminal ganglion. Furthermore, both treatments showed a higher expression of Cannabinoid-type 1 (CB1) receptor in the trigeminal ganglion compared to CCI-IoN rats. Our results show that no difference was observed between groups. We showed that PBM or VBC regulates neuroinflammation and reduces inflammatory protein expression. However, the combination of PBM and VBC did not enhance the effectiveness of both therapies alone.


Novel polyhydroxysterols from the Red Sea marine sponge Lamellodysidea herbacea.
Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of four novel polyhydroxysteroids: cholesta-8-en-3beta,5alpha,6alpha,25-tetrol (1), cholesta-8(14)-en-3beta,5alpha,6alpha,25-tetrol (2), cholesta-8,24-dien-3beta,5alpha,6alpha-triol (3), and cholesta-8(14),24-dien-3beta,5alpha,6alpha-triol (4). Their structures were identified through 1D and 2D NMR studies. Relative stereochemistries were established by analysis of chemical shifts, coupling constants, and NOESY correlations. Compounds 3-4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 microg/disc, respectively.


Safety and efficacy of two repeated cycles of ulipristal acetate in the management of symptomatic uterine fibroid among Indian women.
To evaluate the safety and efficacy along with the impact on uterine and fibroid vascular indices of 2 repeat 12-week courses of ulipristal acetate (UPA) among Indian women. Ninety-four premenopausal women aged 18-45 years with at least 1 symptomatic fibroid of size ranging from 1 cm to 10 cm were included in the study. All participants received 2 courses of 5 mg of UPA orally for 12 weeks starting from the 5th day of their menstrual cycle with a 2-menstrual-cycle break in between. The efficacy was measured in terms of time to amenorrhoea, percentage of women who achieved amenorrhoea for the last 35 consecutive days, reduction in uterine and fibroid volume, as well as its vascularity at the end of the first and second treatment cycle. Eighty-six women completed the first treatment cycle whereas only 65 women completed the second treatment course. Seventy-nine per cent of women achieved amenorrhoea for 35 consecutive days during the first treatment cycle. Median time to amenorrhoea was 7 days and 5 days during the first and second treatment cycle, respectively. Percentage reduction of the mean fibroid volume was 32% and 52% after the first and second treatment cycle, respectively. We observed an increase in fibroid vascular indices (pulsatility index and resistive index) suggesting reduction in fibroid vascularity. Serum oestradiol remained at mid-follicular phase. No serious drug emergent side effect was noted. Two interrupted repeat course of 5mg UPA is well tolerated efficient and safe in symptomatic fibroid among Indian women.


Distribution of apoB/apoA-1 ratio and blood lipids in Sami, Kven and Norwegian populations: the SAMINOR study.
To assess the distribution of blood lipids, lipoprotein and apoB/apoA-1 ratio in a multi-ethnic population of Sami, Kvens and Norwegians in Norway. Study design. A population-based cross-sectional study was carried out in 2003-2004 in an area with a mixed Sami, Kvens/Finns and Norwegian population, the SAMINOR study. A self-administrated questionnaire was distributed and total cholesterol, HDL cholesterol, triglycerides, apoB and apoA-1 counts were analysed in 6461 women and 5772 men between the ages of 36 and 79. In 36-64 age group, Sami men and women had the highest apoB/apoA-1 ratio of the ethnic groups. The ethnic differences remained after adjustment for waist hip ratio, cigarette smoking, systolic and diastolic pressures, alcohol consumption, physical activity during leisure time and family history of myocardial infarction (MI). There were no significant ethnic differences in apoB/apoA-1 ratio in the older age group. Total cholesterol was significantly lower among Sami men and women, aged 65-79 years, than among the Norwegian. The opposite occurred in the 36-49 age group, with higher levels in the Sami population. We found no ethnic differences in HDL cholesterol and triglycerides. Middle-aged Sami women and men have increased levels of apoB/apoA-1 ratio and total cholesterol compared with Norwegians.


Physicochemical study of the formation of complexes between pancreatic proteases and polyanions.
The formation of insoluble complexes between proteins and oppositely charged polyelectrolytes was assessed. Two pancreatic enzymes: trypsin and chymotrypsin, and two anionic synthetic polyelectrolytes: polyacrylate and polyvinylsulfonate, were used for the study at the pH range between 3.00 and 5.00. Two different titration curve shapes, representing two insoluble complexes formation mechanisms, were found. The turbidity of enzyme-polyelectrolyte mixtures is related to the increase either in the size or in the quantity of the insoluble complexes. Ionic strength destabilized insoluble complex formation. Finally, the kinetics of the process of insoluble complex formation at different conditions was studied.


Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.
The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.


Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.
Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. PROSPERO (CRD42019128790).


Use of electroporation to study the cytotoxic effects of fluorodeoxyuridylate in intact cells.
The introduction of 2'-deoxyuridine 5'-monophosphate and its analog, 5-fluoro-2'-deoxyuridine 5'-monophosphate, into intact CCRF-CEM and NIH3T3 cells was achieved by electroporation. Following electroporation, cells were shown to be fully functional as monitored by the incorporation of deoxyuridylate, after conversion to thymidylate, into DNA. Pretreatment of cells with fluorodeoxyuridine completely abolished this effect. In contrast, introduction of the fluoro analog into cells by electroporation markedly inhibited both DNA synthesis and cell growth in a time-dependent manner. Thus, electroporation offers a powerful tool to permeabilize cells to a variety of cellular metabolites and antimetabolites.


Intermittent scanning continuous glucose monitoring is safe and useful in postsurgical glucose monitoring after pancreatoduodenectomy.
Intermittently scanned continuous glucose monitoring (isCGM) systems have not been thoroughly evaluated during in-hospital stay, and there are concerns about accuracy during various conditions. Patients undergoing pancreatoduodenectomy have an increased risk of hyperglycaemia after surgery which is aggravated by parenteral nutrition therapy. This study aims to evaluate glycaemic control and safety during insulin infusion in a surgical non-ICU ward, using a hybrid glucose monitoring approach with isCMG and periodic point-of-care (POC) testing. We prospectively included 100 patients with a resectable pancreatic tumour. After surgery, continuous insulin infusion was initiated when POC glucose was > 7 mmol/l and titrated to maintain glucose between 7 and 10 mmol/l. Glucose was monitored with isCGM together with intermittent POC, every 3-6 h. Median absolute relative difference (MARD) and hypoglycaemic events were evaluated. Mean glucose was compared with a historic control (n = 100) treated with multiple subcutaneously insulin injections, monitored with POC only. The intervention group (isCGM/POC) had significantly lower POC glucose compared with the historic control group (8.8 ± 2.2 vs. 10.4 ± 3.4 mmol/l, p < 0.001). MARD was 17.8% (IQR 10.2-26.7). isCGM readings were higher than POC measurements in 91% of the paired cases, and isCGM did not miss any hypoglycaemic event. About 4.5% of all isCGM readings were < 3.9 mmol/l, but only six events were confirmed with POC, and none was < 3.0 mmol/l. A hybrid approach with isCGM/POC is a safe and effective treatment option in a non-ICU setting after pancreatoduodenectomy.


MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders.
There have been relatively few quantitative MRI studies of temporal lobe structures and the lateral ventricles in bipolar patients and a lack of agreement across studies as to whether these structures differ significantly in size from control subjects. Also there have been no quantitative MRI studies of bipolar II patients. The present study measured temporal lobe and ventricular structures in both bipolar I and bipolar II patients, as well as control subjects. Twenty-five bipolar I patients, 22 bipolar II patients and 19 control subjects underwent MRI brain scans. The 5 mm coronal slices of each subject were coded and measured by a rater who was blind with respect to subject diagnosis. Volume estimates of the temporal lobe and hippocampus were calculated for each hemisphere by measuring the area of the structure in each slice in which it appears, multiplying by 5 mm and summing. In addition to these volume estimates, the area of the lateral ventricle and the inferior horn of the lateral ventricle, the lateral ventricle to cerebrum area ratio (LV/C) and the temporal lobe to cerebrum area ratio (TL/C), were calculated for each hemisphere in one reference slice only. The area of the third ventricle was also measured. Volume estimates and area ratios were then compared among diagnostic groups. There were no significant differences in temporal lobe or hippocampal volume estimates, in the third ventricle and inferior horn of the lateral ventricle area measurements, and in the TL/C area ratio among diagnostic groups. The lateral ventricle area and LV/C area ratio were significantly larger in bipolar I patients than either bipolar II patients or control subjects only in the left hemisphere. Furthermore, these measures were approximately twice as large in the bipolar I patients as the other groups. The current study adds to a growing literature that bipolar I disorder, particularly in males, may show different neurobiological alterations compared to bipolar II patients or control subjects. The pathophysiologic implications of this accumulating evidence of increased left ventricular size in bipolar I disorder remains to be further elucidated.


Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.
Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (p<0.001 for both comparisons) and were lower in patients with lipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (p<0.001), and no differences were found according to the presence of lipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.


Effects of collimator jaw setting on dose output for treatments with multileaf collimator.
The variations in dose output with collimator jaw setting have been investigated for treatment fields shaped by a multileaf collimator. Measurements have been made for 6 and 15 MV x-ray beams on a Varian Clinac 2100C machine. The results of our study show that the collimator jaw settings can affect the dose by about 5% for a small field shaped by a multileaf collimator. The effect is smaller for larger fields.


Self-Assembly of Partially Oxidized Pillar[5]arene into Fibrous Structures.
Partial oxidation of the pillar[5]arene macrocycle with Fe(III) leads to the isolation of a fibrous purple solid with high porosity. Experimental and computational data indicate that the solid material is primarily composed of macrocycles in which two of the hydroquinone units have been oxidized to benzoquinone units. Self-assembly takes place through the formation of multiple quinhydrone charge-transfer complexes between hydroquinone and benzoquinone units on adjacent macrocycles, providing a rare example of self-assembly based on a pentagonal molecular symmetry.


Self-medication practices among pregnant women in Ethiopia.
Self-medication is a worldwide issue that requires special attention due to the potentially harmful effects it can have not only on pregnant women but also on the fetus. This study assessed the magnitude of self-medication practice and associated factors among pregnant women following antenatal care (ANC) in primary healthcare settings in the North Wollo Zone of Ethiopia. An institutional-based cross-sectional study was conducted on 395 pregnant mothers who attended ANC follow-up in selected health centers in the North Wollo Zone of Ethiopia from April 20 to May 20, 2021. A multi-stage sampling method was employed to enroll participants. A face-to-face structured interview was conducted to collect the data. A logistic regression analysis was used to determine the factors associated with self-medication practice. A p value < 0.05 at the 95% confidence level was considered statistically significant. Out of a total of 444 participants approached, 395 (89%) participated in the study. Of these, 44.6% reported practicing self-medication during the current pregnancy. Age < 35 (AOR = 2.18, 95% CI 1.02-9.15; p = 0.032), rural residence (AOR = 3.01, 95% CI 1.43-10.19; p = 0.017), and previous medication use (AOR = 5.02, 95% CI 1.24-12.93; p = 0.015) were found to have a significant association with self-medication practice. Self-medication was highly prevalent among pregnant women in the study setting and result indicates need for critical action. Younger rural women with a history of self-medication use should be provided counselling to find a prescription medication, and measures are needed to minimize self-medication related harm in pregnant women.


Epileptiform activity induced metaplasticity impairs bidirectional plasticity in the hippocampal CA1 synapses via GluN2B NMDA receptors.
Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. Cognitive impairment and memory consolidation problems are common among TLE patients. To understand the changes in the cellular process of memory in TLE, we studied the long-term depression (LTD) in Schaffer-collateral (Sc) CA1 synapses in an epilepsy model. Long-term potentiation (LTP) was investigated in patient samples and animal models by several groups, but LTD was not studied with the same interest in epilepsy research. Here we induced epileptiform activity in rat hippocampal slices using magnesium-free high-potassium (7.5 mM K +) artificial cerebrospinal fluid (HK-ACSF) and characterized the LTD in Sc-CA1 synapses. We found that epileptiform activity abolished/impaired LTD and depotentiation in the Sc-CA1 synapses. In control slices, application of NMDA (30 μM for 3 min) induced chemical LTD (c-LTD) in Sc-CA1 synapses, whereas epileptiform activity induced slices showed slow onset potentiation. Induction of LTD using 1 Hz, 900 pulses yielded a similar outcome as c-LTD. Both forms of LTD were NMDA receptor dependent. In addition, we found that the polarity changes in the synaptic plasticity in epileptiform-induced slices were blocked by GluN2B antagonists ifenprodil and Ro 25-6981. Our data suggest that epileptiform-induced metaplasticity inhibits LTD in Sc-CA1 synapses. We provide new insight into the cellular mechanism of memory formation during epilepsy.


Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor.
The pregnane X receptor (PXR) detects the presence of a wide variety of endogenous and xenobiotic compounds, and is a master regulator of the expression of genes central to drug metabolism and excretion. We present the 2.0A crystal structure of the human PXR ligand-binding domain (LBD) in complex with the cholesterol-lowering compound SR12813 and a 25 amino acid residue fragment of the human steroid receptor coactivator-1 (SRC-1) containing one LXXLL motif. PXR crystallizes as a homodimer in the asymmetric unit in this structure and possesses a novel alpha2 helix adjacent to its ligand-binding cavity. The SRC-1 peptide forms two distinct helices and binds adjacent to the ligand-dependent transactivation AF-2 helix on the surface of PXR. In contrast with previous PXR structures, in which SR12813 bound in multiple orientations, the small SR12813 agonist in this structure binds in a single, unique orientation within the receptor's ligand-binding pocket and contacts the AF-2 helix. Thermal denaturation studies reveal that the SR12813 ligand and SRC-1 coactivator peptide each stabilize the LBD of PXR, and that together they exert an additive effect on the stability of the receptor. These results indicate that the binding of coactivator to the surface of PXR limits the ability of this promiscuous receptor to "breathe" and helps to trap a single, active conformation of SR12813. They further reveal that specificity is required for PXR activation.


Association between tangential beam treatment parameters and cardiac abnormalities after definitive radiation treatment for left-sided breast cancer.
To examine the association between radiation treatment (RT) parameters, cardiac diagnostic test abnormalities, and clinical cardiovascular diagnoses among patients with left-sided breast cancer after breast conservation treatment with tangential beam RT. The medical records of 416 patients treated between 1977 and 1995 with RT for primary left-sided breast cancer were reviewed for myocardial perfusion imaging and echocardiograms. Sixty-two patients (62/416, 15%) underwent these cardiac diagnostic tests for cardiovascular symptoms and were selected for further study. Central lung distance and maximum heart width and length in the treatment field were determined for each patient. Medical records were reviewed for cardiovascular diagnoses and evaluation of cardiac risk factors. At a median of 12 years post-RT the incidence of cardiac diagnostic test abnormalities among symptomatic left-sided irradiated women was significantly higher than the predicted incidence of cardiovascular disease in the patient population, 6/62 (9%) predicted vs. 24/62 (39%) observed, p = 0.001. As compared with patients with normal tests, patients with cardiac diagnostic test abnormalities had a larger median central lung distance (2.6 cm vs. 2.2 cm, p = 0.01). Similarly, patients with vs. without congestive heart failure had a larger median central lung distance (2.8 cm vs. 2.3 cm, p = 0.008). Contemporary RT for early breast cancer may be associated with a small, but potentially avoidable, risk of cardiovascular morbidity that is associated with treatment technique.