Stroke following Glenn anastomosis in a child with inherited thrombophilia.
The optimal anticoagulation following Fontan operation and its modifications remain controversial and it is even less well defined as regards patients with inherited thrombophilia. We present a case of a child with bidirectional Glenn anastomosis for double inlet left ventricle that suffered a stroke despite aspirin prophylaxis; the patient was combined homozygous for prothrombin G20210A mutation and for methylenetetrahydrofolate reductase C677T mutation as well. The family history was positive for fetal loss and premature cardiovascular disease. Large-scale studies are needed to evaluate whether carriers of thrombophilia mutations need more intense thromboprophylaxis.


Membrane trafficking at the ER/Golgi interface: functional implications of RhoA and Rac1.
N-WASP and Arp2/3, the components of the actin nucleation/polymerization signaling pathway governed by Cdc42, are located in Golgi membranes and regulate ER/Golgi interface protein transport. In the present study, we examined whether RhoA and Rac1, like Cdc42, are also involved in this early secretory pathway. Unlike Cdc42, RhoA and Rac1 were not observed in the Golgi complex of different clonal cell lines nor were they present in isolated Golgi membranes. Expression of constitutively active or inactive mutants of RhoA or Rac1 proteins in HeLa cells did not alter either the disassembly or the assembly of the Golgi complex following the addition or withdrawal of BFA, respectively, the ER-to-Golgi VSV-G transport or the Sar1(dn)-induced ER accumulation of Golgi proteins. Moreover, unlike Cdc42-expressing cells, the 15 degrees C-induced subcellular redistribution of the KDEL receptor remained unaltered. Only cells that constitutively express the activated Cdc42 mutant (Cdc42Q61L), or that were microinjected with activated Cdc42Q61L protein, exhibited a significant change in Golgi complex morphology. Collectively, our results demonstrate that RhoA and Rac1 are not located in the Golgi complex, nor do they directly or indirectly regulate membrane trafficking at the ER/Golgi interface. This finding, in turn, confirms that Cdc42 is the only Rho GTPase to have a specific function on the Golgi complex.


Technologies and Standardization in Research on Extracellular Vesicles.
Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component of a variety of physiological and pathological processes. Potential applications of EVs in novel diagnostic and therapeutic strategies have brought increasing attention. However, EV research remains highly challenging due to the inherently complex biogenesis of EVs and their vast heterogeneity in size, composition, and origin. There is a need for the establishment of standardized methods that address EV heterogeneity and sources of pre-analytical and analytical variability in EV studies. Here, we review technologies developed for EV isolation and characterization and discuss paths toward standardization in EV research.


The neuropathologic effects in rats and neurometabolic effects in humans of large-dose remifentanil.
Given in clinically relevant large doses to rats, mu-opioids produce limbic system hypermetabolism and histopathology. This investigation extends these observations, in both rats and humans, for the short-acting drug remifentanil, which allows more precise control and assessment of the effects of duration of opioid exposure. We performed two series of experiments: one in rats for neuropathologic effects and the second in humans for neurometabolic effects. Fifty mechanically ventilated rats received saline solution or remifentanil 20-160 microg x kg(-1) x min(-1) for 3 h, followed by neuropathologic evaluation 7 days later. Four volunteers underwent induction of anesthesia and endotracheal intubation with propofol and rocuronium administration followed by remifentanil infusion at 1-3 microg x kg(-1) x min(-1) with positron emission tomography evaluation of cerebral metabolic rate for glucose. In rats, dose-related electroencephalogram activation was evident and 19 of 40 remifentanil-treated rats showed brain damage, primarily in the limbic system (P < 0.01). In humans, cerebral metabolic rate for glucose in the temporal lobe increased from 6.29 +/- 0.32 to 7.68 +/- 1.05 mg x 100 g(-1) x min(-1) (P < 0.05). These data indicate that prolonged large-dose remifentanil infusion is neurotoxic in rats with congruent metabolic effects with brief infusion in humans and suggest that some adverse effects reported in rats may be clinically relevant. This study demonstrates dose-related remifentanil neurotoxicity in physiologically controlled rats with congruent brain metabolic effects in four humans undergoing positron emission tomography evaluation during brief large-dose remifentanil anesthesia. These data suggest that some adverse effects reported in rats may be clinically relevant.


[A case of cerebral vascular disease associated with prosopagnosia and minor hemisphere syndrome (author's transl)].
A case of "apractognosia", a syndrome of minor hemisphere, and prosopagnosia was described. A 68 years old, right handed, hypertensive man who had experienced an episode of left hemiparesis of several weeks' duration developed a syndrome of minor hemisphere, metamorphopsia, visuoconstructive disability, spatial dysgraphia, topographical and geographical disorientation and dressing apraxia, with associated left homonymous hemianopsia. A right occipital lesion was disclosed by an isotopic brain scan and a CT scan. The CT scan also disclosed a generalized cerebral atrophy. Memory disturbance, both verbal and visual, was observed. Verbal memory was examined by coupled words test, digit span and 10-words learning test, and visual memory by spatial pointing span and memorizing unfamiliar faces. The patient was able to differentiate unfamiliar faces, but was not able to memorize them correctly. Although the patient has complained of a disturbance of recognizing familiar faces (prosopagnosia), but actually, sometimes he was able to recognize the members of his family by the faces and sometimes he was not. He has stated that he could not recall familiar faces. The authors suggested prosopagnosia is, as Benton (1975) has supposed, considered to be the limited disorders of memory and association.


Freeze-drying of enzymes in case of water-binding and non-water-binding substrates.
Enzymes typically have a critical instability, which dominates both formulation and process development. In this paper, the ability to preserve the enzyme activity during freeze-drying was investigated for both water-binding and non-water-binding substrates. For this purpose, acid phosphatase was used as model protein. In addition, a procedure for the fast development of a freeze-drying cycle is shown. For the secondary drying part, the effect of processing temperature and time on enzyme activity was investigated. The enzyme activity decreased continuously during secondary drying, with a dramatic drop associated with processing temperatures higher than 293 K. Besides product temperature, the residual moisture level and water mobility are also important. As the residual moisture level and water mobility depend on the product formulation, the stabilizing effect against the enzyme deactivation was studied for a number of formulations which contain different additives, that is, sucrose, lactose, mannitol, and poly-vinylpyrrolidone, with a dramatic activity loss associated with crystallizing excipients. This study also confirmed that not all water-binding substrates can successfully protect the enzyme against deactivation. In fact, water-binding substrates containing reducing sugars (lactose) showed the highest loss of activity.


Adverse reactions to Bactrim--a retrospective view.
A historical survey based on the most important literature is presented as a starting point for further discussion on the significance of possible adverse reactions reported after prescription of cotrimoxazole. The often changing and contradictory assessments made of the situation in different countries and at different times are outlined, and the difficulty of making a balanced and just evaluation of long established drugs is shown, particularly if the available data are derived primarily from spontaneous reports which, besides being almost impossible to verify, are often incomplete.


Proteochemical, immunological and enzymatic properties of two amylase components from human pancreatic juice.
Two amylase components were purified from human pancreatic juice and investigated for their proteochemical, immunological and enzymatic properties. The two components were similar in molecular weight, amino acid composition and immunoreactivity as determined by radioimmunoassay for the major component of pancreatic amylase. Their specific activity, optimal pH value, and stability were identical. Both were equally activated by chloride ion and their hydrolysis modes of various substrates were also identical. The only difference found between them was in the electrophoretic mobility in the peptide map, indicating that the difference was brought about by deamidation. The quantitative analysis of pancreatic amylase isozymes can provide information on the posttranslational modification in pancreatic tissue and/or in body fluids.


Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing.
An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin's mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche.


Calcination of sewage sludge-based sulphoaluminate cement clinker: Mineral formation mechanism and heavy metal transition behaviors.
Utilizing sewage sludge (SS) to calcinate sulphoaluminate cement (SAC) is a promising technology for low-carbon transition of cement industry, but the unclear effects of SS-contained heavy metals limit the application of this technology. In this study, the effects of SS addition on the calcination of SAC clinker and the transformation of heavy metals were studied from the aspects of mineral phase change, microstructure evolution and heavy metal speciation respectively, covering the mineral formation temperature 900-1250 °C. The results show that the added SS will reduce the formation temperature and change the reaction pathways of mineral phases. When the content of SS increases from 10% to 25%, the compositions of mesophases CaO·Al2O3 and 4CaO·2SiO2·CaSO4 increase by 6.33% and 9.73%, respectively. Meanwhile, the formation of minerals will solidify Zn, Ni, Mn, Cu, Cr, and convert them into a more stable fraction (residual fraction), indicating a lower probability to harm the environment. Moreover, heavy metals present different migration behaviors. After calcination, Mn migrates from SS to 4CaO·Al2O3·Fe2O3 (52.48%), while Zn prefers to enter 3CaO·3Al2O3·CaSO4 (43.74%) and 4CaO·Al2O3·Fe2O3 (38.06%). This study offers new insights into the mineral formation mechanism and heavy metal transition behaviors of sewage sludge-based SAC.


The Acetabular Fracture Prognostic Nomogram: Does it Work for Fractures of the Posterior Wall?
A recently proposed nomogram is an attempt to define the subset of acetabular fractures at risk for primary total hip arthroplasty (THA) within 2 years of open reduction and internal fixation (ORIF). Our objectives were to determine whether this nomogram provides information adequate to reliably (1) prognosticate outcome within 2 years after ORIF or (2) identify optimal initial treatment choice (THA vs. ORIF) for patients with a posterior wall fracture. Retrospective case series. University level 1 Trauma Center. From a database of consecutive posterior wall fractures treated by ORIF, 103 patients were identified for analysis: 6 with an unsatisfactory result at less than 2 years and 97 followed 2-14 years. Calculation of percent risk of requiring THA within 2 years using the nomogram. Comparison of this percent risk to the actual clinical outcome within 2 years after ORIF, measured in 2 ways: (1) THA performed (5 patients) and (2) overall unsatisfactory hip function determined by the modified Merle d'Aubigné score (9 patients total: the 5 with THA plus 4 additional without THA but having unsatisfactory hip function). The calculated percent risk ranged widely, with much overlap among patients having satisfactory or unsatisfactory results of ORIF. Statistical analysis did not yield a clinically useful positive predictive value: 0.25 [95% confidence interval (CI), 0.08-0.53] for THA and 0.44 (95% CI, 0.21-0.69) for an overall unsatisfactory clinical result. The acetabular fracture prognostic nomogram in its current form does not provide sufficient information to prognosticate outcome after ORIF or to determine appropriate surgical management for posterior wall fractures. Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.


Prolapsed thoracic intervertebral disc: the importance of CT assisted myelography.
We present six new cases of prolapsed thoracic intervertebral disc (PTIVD), and review the clinical and radiological features, particularly with regard to the role of computed tomography (CT) examination in the diagnosis and management. In patients with atypical lower limb pain, particularly when associated with sphincter disturbances, lumbar myelography is incomplete unless supplemented by an examination of the conus region and lower thoracic cord. The supplementary use of CT in suspected PTIVD is of considerable value to the surgeon in determining the size, position, and volume of the sequestration, and the extent of excavation of the spinal cord by prolapsed disc material.


Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients.
Using cerebral microdialysis, baseline values for energy-related chemical markers have been reported in awake patients. Radionuclide studies have demonstrated a locally decreased metabolism, thought to be the result of brain retraction. These baseline values, however, may not be applicable to patients after surgical aneurysm repair following a subarachnoid hemorrhage (SAH). We assessed metabolic chemical marker levels in World Federation of Neurological Surgeons Committee (WFNS) grade I SAH patients after aneurysm surgery and compared them with previously reported baseline values. In 5 WFNS grade I SAH patients, energy-related chemical marker levels were obtained using microdialysis in the area of brain retraction after aneurysm surgery. In addition, an [(18)F]2-deoxy-d-glucose positron emission tomography (FDG-PET) was performed. The FDG-PET showed a decrease of glucose metabolism in the frontotemporal area. Comparing the mean values for chemical markers of this study with reported baseline values, the most striking difference was a mild decrease of pyruvate and an increase of the lactate/pyruvate ratio. In individual patients, some markers indicated possible ischemia. A consistent pattern or ischemic profile for all markers, however, was not found. FDG-PET scanning confirmed postoperative metabolic changes found in previous studies. Mean interstitial chemical marker levels ranged from normal to mildly deviant compared with reference chemical marker levels for awake patients and are likely to be applicable in SAH patients after aneurysm repair.


Carotid Endarterectomy on Antiplatelet Agents in the Era of Point-of-Care Testing.
The safety of carotid endarterectomy in patients with a response to antiplatelet agents (aspirin and clopidogrel) confirmed by point-of-care testing is unknown. Thus, we sought to determine whether using point-of-care assessment of platelet inhibition reveals risk factors for operative complications or predicts clinical outcomes. We reviewed records of carotid endarterectomy patients treated from March 2013 to July 2015 to extract demographics, lesion characteristics, laboratory data, procedural complications, and follow-up. Administration of aspirin, clopidogrel, or therapeutic anticoagulation within 5 days before surgery was recorded. We analyzed 79 patients with 86 lesions (mean age 70.9 ± 10.0 years). More patients with a P2Y12 reaction unit (PRU) <170 had neck hematomas (4/10, 40.0%) than those with a PRU ≥170 (2/9, 22.2%) (P = 0.63). Estimated blood loss ≥100 mL was more frequent among patients with PRU <170 (9/10, 90.0%) than among those with PRU ≥170 (5/9, 55.6%) (P = 0.09). Clopidogrel use, regardless of response, independently predicted neck hematoma in a logistic regression model, with increased odds of 8.5. Mean postoperative modified Rankin Scale scores did not differ statistically between clopidogrel users and nonusers at a mean follow-up of 108.5 ± 146.3 days (P = 0.27). Clopidogrel use within 5 days of carotid endarterectomy independently predicted postoperative neck hematomas, most of which were managed conservatively. Patients with PRU <170 were more likely to have estimated blood loss ≥100 mL during surgery and surgery lasting ≥3 hours.


Blunt pancreatic trauma: A Western Trauma Association critical decisions algorithm.
The Western Trauma Association (WTA) has undertaken publication of best practice clinical practice guidelines on multiple trauma topics. These guidelines are based on scientific evidence, case reports, and best practices per expert opinion. Some of the topics covered by this consensus group do not have the ability to have randomized controlled studies completed because of complexity, ethical issues, financial considerations, or scarcity of experience and cases. Blunt pancreatic trauma falls under one of these clinically complex and rare scenarios. This algorithm is the result of an extensive literature review and input from the WTA membership and WTA Algorithm Committee members. Multiple evidence-based guideline reviews, case reports, and expert opinion were compiled and reviewed. The algorithm is attached with detailed explanation of each step, supported by data if available. Blunt pancreatic trauma is rare and presents many treatment challenges.


Synthesis and characterization of a bovine hexokinase 1 cDNA probe by mixed oligonucleotide primed amplification of cDNA using high complexity primer mixtures.
Hexokinase (EC 126.96.36.199) catalyzes the first step in glucose metabolism, using ATP for the phosphorylation of glucose to glucose 6-phosphate. A portion of the HK1 gene was cloned by mixed oligonucleotide primer amplification of cDNA using primers of high complexity. The amino acid sequence for a partial fragment of bovine cardiac muscle HK was determined and used to create primer mixtures of 256- and 1024-fold complexity. Two products were generated from bovine cardiac muscle cDNA which show 82% nucleotide and 93% amino acid identity with a region of rat brain HK1 and cDNA. This work demonstrates that extension and amplification of cDNA probes may be successful even when amino acid sequence data indicate substantial codon degeneracy.


Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes.
The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/- 3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.


Macrophage expression of LRP1, a receptor for apoptotic cells and unopsonized erythrocytes, can be regulated by glucocorticoids.
Macrophage phagocytosis of apoptotic cells, or unopsonized viable CD47(-/-) red blood cells, can be mediated by the interaction between calreticulin (CRT) on the target cell and LDL receptor-related protein-1 (LRP1/CD91/α2-macroglobulin receptor) on the macrophage. Glucocorticoids (GC) are powerful in treatment of a range of inflammatory conditions, and were shown to enhance macrophage uptake of apoptotic cells. Here we investigated if the ability of GC to promote macrophage uptake of apoptotic cells could in part be mediated by an upregulation of macrophage LRP1 expression. Using both resident peritoneal and bone marrow-derived macrophages, we found that the GC dexamethasone could dose- and time-dependently increase macrophage LRP1 expression. The GC receptor-inhibitor RU486 could dose-dependently prevent LRP1 upregulation. Dexamethasone-treated macrophages did also show enhanced phagocytosis of apoptotic thymocytes as well as unopsonized viable CD47(-/-) red blood cells, which was sensitive to inhibition by the LRP1-agonist RAP. In conclusion, these data suggest that GC-stimulated macrophage uptake of apoptotic cells may involve an upregulation of macrophage LRP1 expression and enhanced LRP1-mediated phagocytosis.


Preventing low birthweight and reduction of child mortality.
Surprisingly little attention is paid to birthweight improvement as a means of reducing child mortality. Half of the 10 million pre-school-age children that die each year have malnutrition as an underlying or associated cause. Furthermore, the majority of these deaths are associated with the mild and moderate forms of malnutrition, reflecting how this effect is manifest across the whole population distribution. Similar relationships are seen between birthweight and neonatal mortality, with the least risk of neonatal death occurring in children born weighing more than 3.5 kg. Child malnutrition is increasingly recognized to be largely determined during the period of fetal and infant growth, when maternal nutrition has its strongest influence. Although the effects of maternal food supplements on mean birthweight are relatively small, because of their influence across the population distribution they have great biological significance. An increase of 100 g in mean birthweight is associated with a 30-50% reduction in neonatal mortality. The programmes that need to be put in place to improve maternal nutritional status are discussed, and the programme initiatives being promoted by UNICEF to prevent low birthweight, including multiple micronutrient supplementation trials are further described.


Fear of Falling in Women with Fibromyalgia and Its Relation with Number of Falls and Balance Performance.
To evaluate fear of falling, number of falls, and balance performance in women with FM and to examine the relationship between these variables and others, such as balance performance, quality of life, age, pain, and impact of fibromyalgia. A total of 240 women participated in this cross-sectional study. Of these, 125 had fibromyalgia. Several variables were assessed: age, fear of falling from 0 to 100, number of falls, body composition, balance performance, lower limb strength, health-related quality of life, and impact of fibromyalgia. Women with fibromyalgia reported more falls and more fear of falling. Fear of falling was associated with number of falls in the last year, stiffness, perceived balance problems, impact of FM, and HRQoL whereas the number of falls was related to fear of falling, balance performance with eyes closed, pain, tenderness to touch level, anxiety, self-reported balance problems, impact of FM, and HRQoL. FM has an impact on fear of falling, balance performance, and number of falls. Perceived balance problems seem to be more closely associated with fear of falling than objective balance performance.


Effect of variations in pressure and flow on the geometry of isolated canine carotid arteries.
A study is described in which the effects of hemodynamics on arterial geometry are investigated in vitro. A novel perfusion apparatus is employed to deliver pulsatile flow through excised canine carotid arteries under carefully controlled conditions. Data of perfused vessel diameter and arterial wall thickness are derived from the radial displacement of the pulsating vessel as measured using a scanning laser micrometer whose accuracy is determined to be 0.0125 mm (0.0005 in). The results of 30 perfusion experiments suggest that the hemodynamic variables of transmural pressure, pulse pressure and flow rate influence vessel size and radial strain. The physiologic implications of these findings are discussed.


Inhibition of arterial thrombosis by a protease-activated receptor 1 antagonist, FR171113, in the guinea pig.
The antiplatelet and antithrombotic effects of FR171113, 3-(4-chlorophenyl)-2-(2,4-dichlorobenzoylimino)-5-(methoxycarbonyl methylene)-1,3-thiazolidin-4-one, a non-peptide protease-activated receptor 1 (PAR1) antagonist, were evaluated in guinea pigs. FR171113 inhibited Ser-Phe-Leu-Leu-Arg-Asn-NH2 (a synthetic PAR1 agonist peptide)-induced and thrombin-induced aggregation of guinea pig platelets in a concentration-dependent manner in vitro (IC50=1.5 and 0.35 microM, respectively). Subcutaneous administration of FR171113 (0.1-3.2 mg/kg) produced a dose-dependent inhibition of platelet aggregation ex vivo. The ED50 value of FR171113 for platelet aggregation was 0.49 mg/kg s.c. However, FR171113 did not have an inhibitory effect on ADP- or collagen-induced platelet aggregation in vitro and ex vivo. One hour after FR171113 treatment at 1.0 mg/kg s.c., significant inhibition of arterial thrombosis without a prolongation of thrombin time or coagulation time was seen in the FeCl3-induced carotid artery thrombosis model in guinea pigs. Furthermore, FR171113 did not prolong bleeding time even at 32 mg/kg s.c., which is a much higher dose than that required in the thrombosis model. These observations indicate that FR171113 has desirable antiplatelet effects both in vitro and in vivo and that its in vivo antithrombotic activity is efficacious without causing a prolongation of bleeding time.


Minimal water exchange with gel immersion: A safe and useful method to secure the visual field during balloon enteroscopy-assisted endoscopic retrograde cholangiography.
During balloon enteroscopy-assisted endoscopic retrograde cholangiography, the minimal water exchange method facilitates reaching the site and prevents pneumobilia, hepatic portal venous gas, and air embolism. However, the water may mix with bile or blood, obscuring the visual field. Yokoyama and colleagues demonstrate how the gel immersion method helps overcome this problem.


Effect of VL and VH consensus sequence-specific primers on the binding and expression of a mini-molecule antibody directed towards human gastric cancer.
To construct ScFv and Fab from murine anti-gastric cancer monoclonal antibody (mAb)3H11. At first, 3H11 ScFv and Fab were constructed with V genes PCR amplified by degenerate primers for FR1. The bacterial expressed 3H11 Ab fragments showed no antigen binding activity. Then, phage antibody library and random mutated library were constructed from 3H11 hybridoma cells and panning selection was perfomed. Again the identification of positive clone was failed. Finally the N-terminal sequences of V regions were resumed to 3H11 original sequences by site-directed mutagenesis via PCR. Binding activity to gastric cancer cells was detected only from N-terminal sequence corrected 3H11 ScFv and Fab,though the expression of the Ab fragments was not affected. Correction of either VL or VH N-terminal sequences could partially resume the antigen binding activity. Sequence changes of V region N terminal introduced by PCR may seriously affect antigen binding without affecting the expression of antibody.


Complete Genome Sequences of Seven Neisseria gonorrhoeae Clinical Isolates from Mucosal and Disseminated Gonococcal Infections.
Neisseria gonorrhoeae is a Gram-negative bacterium that causes the sexually transmitted infection gonorrhea. N. gonorrhoeae has progressively developed resistance to all currently prescribed antibiotics, and no vaccine is available. Here, we report the closed, completed, annotated genome sequences for seven N. gonorrhoeae strains obtained by single-molecule real-time (SMRT) long-read genome sequencing.


Internet use and physical activity of older adults during the COVID-19 pandemic: a cross-sectional study in a northern Japanese City.
Little is known of whether Internet use is associated with physical activity among socially isolated older adults during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated the association between Internet use and physical activity, and whether this association differs depending on social isolation among community-dwelling Japanese older adults. A cross-sectional study was conducted with 1048 community-dwelling residents aged 65-90 years. Data were obtained using a self-reported questionnaire in August 2020. Physical activity was assessed using the International Physical Activity Questionnaire-Short Form. Multivariable logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between Internet use and moderate-to-vigorous physical activity (MVPA). Internet use showed a significant association with MVPA (OR = 1.42, 95% CI: 1.06-1.90) after adjusting for age, sex, self-reported socioeconomic status, and other health-related characteristics. When the results were stratified by social participation and living status, Internet use was associated with a significantly higher likelihood of MVPA among participants with no social participation (OR = 1.81, 95% CI: 1.03-3.17) and living with family (OR = 1.40, 95% CI: 1.02-1.93). Internet use was associated with sufficient physical activity, and this association may differ depending on the social isolation among community-dwelling older adults in Japan.


Exploring N-myristoyltransferase as a promising drug target against parasitic neglected tropical diseases.
Neglected tropical diseases (NTDs) constitute a group of approximately 20 infectious diseases that mainly affect the impoverished population without basic sanitation in tropical countries. These diseases are responsible for many deaths worldwide, costing billions of dollars in public health investment to treat and control these infections. Among them are the diseases caused by protozoa of the Trypanosomatid family, which constitute Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), and Leishmaniasis. In addition, there is a classification of other diseases, called the big three, AIDS, tuberculosis, and malaria, which are endemic in countries with tropical conditions. Despite the high mortality rates, there is still a gap in the treatment. The drugs have a high incidence of side effects and protozoan resistance, justifying the investment in developing new alternatives. In fact, the Target-Based Drug Design (TBDD) approach is responsible for identifying several promising compounds, and among the targets explored through this approach, N-myristoyltransferase (NMT) stands out. It is an enzyme related to the co-translational myristoylation of N-terminal glycine in various peptides. The myristoylation process is a co-translation that occurs after removing the initiator methionine. This process regulates the assembly of protein complexes and stability, which justifies its potential as a drug target. In order to propose NMT as a potential target for parasitic diseases, this review will address the entire structure and function of this enzyme and the primary studies demonstrating its promising potential against Leishmaniasis, T. cruzi, T. brucei, and malaria. We hope our information can help researchers worldwide search for potential drugs against these diseases that have been threatening the health of the world's population.


Lead-Free Metal Halide Perovskites and Perovskite Derivatives as an Environmentally Friendly Emitter for Light-Emitting Device Applications.
Recently, newly emerging lead halide perovskites have attracted great attention as a new class of light emitters in luminescent devices because of their superior photoluminescence quantum yield, adjustable emission wavelength, high charge-carrier transport ability, and low-temperature processing technique. However, the poor stability and lead toxicity of such materials severely restrict their practical applications and future commercialization. Therefore, recent efforts have been devoted to developing lead-free metal halide perovskites and their derivatives to address the above hurdles. In this Perspective, we first review the recent progress on the lead-free metal halide materials and their optical properties. We then discuss the stability issues of lead-free perovskites against heat, ultraviolet light, oxygen, and moisture. Further, we give a demonstration of the preliminary achievements and limitations in lead-free material-based light-emitting devices. Finally, we present current existing challenges and possible development opportunities in this field based on lead-free material systems.


Proapoptotic Bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death.
Recent evidence indicates that the mitochondrial lipid cardiolipin may be instrumental in the proapoptotic action of Bcl-2 family proteins on mitochondrial membranes, leading to the release of apoptogenic factors. However, contrasting evidence indicates that progressive loss of cardiolipin occurs during apoptosis. Here we show that Bid, a crucial proapoptotic protein that integrates the action of other Bcl-2 family members, exhibits discrete specificity for metabolites of cardiolipin, especially monolysocardiolipin (MCL). MCL, normally present in the remodelling of mitochondrial lipids, progressively increases in mitochondria during Fas-mediated apoptosis as a by-product of cardiolipin degradation, and also enhances Bid binding to membranes. MCL may thus play a crucial role in connecting lipid metabolism, relocation of Bid to mitochondria and integrated action of Bcl-2 proteins on mitochondrial membranes. We propose that Bid interaction with MCL 'primes' the mitochondrial outer membrane via segregation of lipid domains, facilitating membrane discontinuity and leakage of apoptogenic factors.


A deep-SIQRV epidemic model for COVID-19 to access the impact of prevention and control measures.
The coronavirus (COVID-19) has mutated into several variants, and evidence says that new variants are more transmissible than existing variants. Even with full-scale vaccination efforts, the theoretical threshold for eradicating COVID-19 appears out of reach. This article proposes an artificial intelligence(AI) based intelligent prediction model called Deep-SIQRV(Susceptible-Infected-Quarantined-Recovered-Vaccinated) to simulate the spreading of COVID-19. While many models assume that vaccination provides lifetime protection, we focus on the impact of waning immunity caused by the conversion of vaccinated individuals back to susceptible ones. Unlike existing models, which assume that all coronavirus-infected individuals have the same infection rate, the proposed model considers the various infection rates to analyze transmission laws and trends. Next, we consider the influence of prevention and control strategies, such as media marketing and law enforcement, on the spread of the epidemic. We employed the PAN-LDA model to extract features from COVID-19-related discussions on social media and online news articles. Moreover, the Long Short Term Memory(LSTM) model and Evolution Strategies(ES) are used to optimize transmission rates of infection and other model parameters, respectively. The experimental results on epidemic data from various Indian states demonstrate that persons infected with coronavirus had a more significant infection rate within four to nine days after infection, which corresponds to the actual transmission laws of the epidemic. The experimental results show that the proposed model has good prediction ability and obtains the Mean Absolute Percentage Error(MAPE) of 0.875%, 0.965%, 0.298%, and 0.215% for the next eight days in Maharashtra, Kerala, Karnataka, and Delhi, respectively. Our findings highlight the significance of using vaccination data, COVID-19-related posts, and information generated by the government's tremendous efforts in the prediction calculation process.


Acetylcholine synthesis and its dependence on nervous activity.
The findings discussed in this paper mainly derived from studies on salivary glands, serving as model organs, indicate that the capacity to form the neurotransmitter acetylcholine, as judged by the activity of choline acetyltransferase, is influenced by the traffic of nerve impulses, as a long term effect. In the glands, choline acetyltransferase seems to be exclusively localized to the cholinergic nerves. In the postganglionic parasympathetic nerves of the glands, the activity of choline acetyltransferase decreases when the flow of secretory impulses in these nerves is abolished or reduced either by isolating the nerves from the central nervous system, surgically or pharmacologically, or by diminishing the reflex activation of the glands from the mouth. The opposite occurs when the reflex activation of the salivary glands is enhanced, i.e. the activity of choline acetyltransferase increases. Observations on various other organs are quoted in support of the view that the traffic of nerve impulses is of importance for the activity of the enzyme. An increase in choline acetyltransferase activity also occurs in some salivary glands after sympathetic denervation. This puzzling observation is discussed in relation to impulse traffic. Increased nerve impulse traffic and collateral sprouting seem to be responsible for the rapid restitution of choline acetyltransferase activity from a low level in an organ partially deprived of its cholinergic nerve supply.


The role of MLC901 in reducing VEGF as a vascular permeability marker in rats with spinal cord injury.
Damaged neural tissue caused by SCI could induce vascular endothelial growth factor (VEGF) that can worsen the condition in the late phase by increasing vascular permeability, thus inducing tissue oedema, which can worsen the infarction. MLC 901 has been widely used in Asia for stroke patients because its mechanism is known to down-regulate VEGF levels in ischemic tissue. Ten Sprague-Dawley rats were used in this experiment. To create a severe spinal cord injury in animal models. The animals were then randomly divided into two groups. MLC 901 was given to the first group, which was the intervention group, and placebo to the second group, which was the control group. This study showed a decrease in the mean VEGF mRNA expression in the group given MLC 901 compared to the control group, which had a very high mean VEGF mRNA expression starting after 1 h of administration of MLC 901 until day 14 after spinal cord injury. In addition, there was a decrease in VEGF levels in the MLC 901 group compared to the control group from 3 h after spinal cord injury (1 h after MLC 901 administration) to 14 days after spinal cord injury. It can be concluded that administration of MLC 901 can reduce vascular permeability, one of the mechanisms that is thought to occur is to reduce VEGF levels. MLC 901 also maintains the neuroprotective effect provided by VEGF by maintaining this level above the basal level until day 14.


Growth in Turner's syndrome: spontaneous and fluoxymesterone stimulated.
Spontaneous growth was analysed in a group of 55 girls with Turner's syndrome and various karyotypes. Their variation in height and its dependence on parental height were similar to that of normal girls. At all ages, the 45,X karyotype was associated with slightly greater mean stature than the other karyotypes together. The bone ages lagged progressively behind from 10 years onwards. Twenty-five patients aged between 9.1 and 17.2 years were given fluoxymesterone, 0.06-0.17 mg/kg daily, for at least 1 year. Their height velocities increased significantly. This brought about a clear psychological benefit. Their final heights were predicted before and after therapy, with a new method based on the spontaneous growth and bone maturation of our patients. The response was individually variable but, on average, the patients gained in predicted height from the therapy. This effect was not lost during a posttreatment year. Abnormal lowering of the voice occurred in patients receiving greater than or equal to 0.15 mg/kg fluoxymesterone daily, but never with less than 0.13 mg/kg. No other adverse effects appeared. Thus, fluoxymesterone is useful for promoting growth in girls with Turner's syndrome.


DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88.
Alu RNA accumulation due to DICER1 deficiency in the retinal pigmented epithelium (RPE) is implicated in geographic atrophy (GA), an advanced form of age-related macular degeneration that causes blindness in millions of individuals. The mechanism of Alu RNA-induced cytotoxicity is unknown. Here we show that DICER1 deficit or Alu RNA exposure activates the NLRP3 inflammasome and triggers TLR-independent MyD88 signaling via IL18 in the RPE. Genetic or pharmacological inhibition of inflammasome components (NLRP3, Pycard, Caspase-1), MyD88, or IL18 prevents RPE degeneration induced by DICER1 loss or Alu RNA exposure. These findings, coupled with our observation that human GA RPE contains elevated amounts of NLRP3, PYCARD, and IL18 and evidence of increased Caspase-1 and MyD88 activation, provide a rationale for targeting this pathway in GA. Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements.


Mitochondrial dysfunction and autophagy activation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats.
The recent rise in illicit use of methamphetamine (METH), a highly addictive psychostimulant, is a huge health care burden due to its central and peripheral toxic effects. Mounting clinical studies have noted that METH use in humans is associated with the development of cardiomyopathy; however, preclinical studies and animal models to dissect detailed molecular mechanisms of METH-associated cardiomyopathy development are scarce. The present study utilized a unique very long-access binge and crash procedure of METH self-administration to characterize the sequelae of pathological alterations that occur with METH-associated cardiomyopathy. Rats were allowed to intravenously self-administer METH for 96 h continuous weekly sessions over 8 weeks. Cardiac function, histochemistry, ultrastructure, and biochemical experiments were performed 24 h after the cessation of drug administration. Voluntary METH self-administration induced pathological cardiac remodeling as indicated by cardiomyocyte hypertrophy, myocyte disarray, interstitial and perivascular fibrosis accompanied by compromised cardiac systolic function. Ultrastructural examination and native gel electrophoresis revealed altered mitochondrial morphology and reduced mitochondrial oxidative phosphorylation (OXPHOS) supercomplexes (SCs) stability and assembly in METH exposed hearts. Redox-sensitive assays revealed significantly attenuated mitochondrial respiratory complex activities with a compensatory increase in pyruvate dehydrogenase (PDH) activity reminiscent of metabolic remodeling. Increased autophagy flux and increased mitochondrial antioxidant protein level was observed in METH exposed heart. Treatment with mitoTEMPO reduced the autophagy level indicating the involvement of mitochondrial dysfunction in the adaptive activation of autophagy in METH exposed hearts. Altogether, we have reported a novel METH-associated cardiomyopathy model using voluntary drug seeking behavior. Our studies indicated that METH self-administration profoundly affects mitochondrial ultrastructure, OXPHOS SCs assembly and redox activity accompanied by increased PDH activity that may underlie observed cardiac dysfunction.


Isolation and characterization of a gene involved in ethylene biosynthesis from Arabidopsis thaliana.
The ethylene forming enzyme (EFE) is a key factor in ethylene biosynthesis. To understand better the regulation of ethylene biosynthesis in vegetative tissues, we set out to isolate and characterize a complementary DNA (cDNA) encoding the EFE from Arabidopsis thaliana. An A. thaliana cDNA library was screened with pTOM 13, a tomato cDNA coding for the EFE. A cDNA clone (pEAT1) was isolated. The cDNA is 1200 nucleotides (nt) in length and predicts a protein of M(r) 36,663. The insert includes the complete open reading frame of 972 bp and shows strong homology with several reported sequences, both at the nt and amino acid level. In whole seedlings, expression of pEAT1 was enhanced by wounding, ethrel, Fe2+, and 1-amino-cyclopropane-carboxylic acid (ACC) treatments. In contrast, heat shock had no effect on the expression.


Circulating steroids in male rats following inhalation of n-alcohols.
The effect of inhaled methanol, ethanol, n-propanol and n-butanol on male reproductive function as measured by the serum concentration of circulating T (testosterone) and LH (luteinizing hormone) has been investigated. The animals were exposed to concentrations of these alcohols equal to the current threshold limit values in industry (methanol: 200 ppm, ethanol: 1000 ppm, n-propanol, n-butanol: 50 ppm) 6 h a day for up to 1 week. A significant depression in the concentration of circulating T was found after the first 6 h exposure to the respective alcohols with restoration after a recovery period of 18 h, except in rats exposed to n-butanol where a depression of 48% could still measured. The concentration of LH was within the normal range in all experimental groups whereas corticosterone was increased after exposure to n-butanol. Exposure for 1 week was not associated with any significant inability of the rat testis to produce T.


Antihypertensive peptides from animal products, marine organisms, and plants.
Bioactive peptides from food proteins exert beneficial effects on human health, such as angiotensin-converting enzyme (ACE) inhibition and antihypertensive activity. Several studies have reported that ACE-inhibitory peptides can come from animal products, marine organisms, and plants-derived by hydrolyzing enzymes such as pepsin, chymotrypsin, and trypsin-and microbial enzymes such as alcalase, thermolysin, flavourzyme, and proteinase K. Different ACE-inhibitory effects are closely related with different peptide sequences and molecular weights. Sequences of ACE-inhibitory peptides are composed of hydrophobic (proline) and aliphatic amino acids (isoleucine and leucine) at the N-terminus. As result of this review, we assume that low molecular weight peptides have a greater ACE inhibition because lower molecular weight peptides have a higher absorbency in the body. Therefore, the ACE-inhibitory effect is closely related with the degree of enzymatic hydrolysis and the composition of the peptide sequence.


Effects of ethidium bromide on the respiratory chain and oligomycin-sensitive adenosine triphosphatase in purified mitochondria from the cellular slime mold Dicyostelium discoideum.
Mitochondria were isolated from the cellular slime mold. Dictyoostelium discoideum, and partially purified by sucrose density gradient fractionation. The most purified mitochondrial fraction from the gradient contained essentially no contaminating lysosomes and minimal amounts of contaminating peroxisomes as determined by the marker enzymes N-acetyl-glucosaminidase and catalase. A mitochondrial fraction with the same amount of lysosomal and peroxisomal contamination was also isolated from cells which had been treated with ethidium bromide for 5 days. The most purified mitochondrial fraction from control and ethidium bromide-treated cells had an identical buoyant density of 1.181 to 1.182 g per ml, suggesting that treatment with the drug does not result in any drastic structural changes in the mitochondrial membrane which would affect its density. In the purified mitochondria from ethidium bromide-treated cells, the content of cytochromes a-a3 was decreased over 80% and that of cytochrome oxidase and oligomycin sensitive ATPase were reduced approximately 50%. By contrast, the specific activities of NADH and succinate dehydrogenases were identical in the purified mitochondria from control and ethidium bromide-treated cells. Previously, we had reported that the specific activities of these two enzymes had nearly doubled in whole cells maintained in ethidium bromide for a time equivalent to six or seven generations after growth had stopped (Stuchell, R. N., Weinstein, B. I., and Beattie, D. S. (1973) Fed. Eur. Biochem. Coc Lett. 37, 23-26). These results suggest that continued formation of new mitochondrial membranes, with an identical complement of succinate and NADH dehydrogenases, must occur despite the cessation of cell growth which occurs as a result of the ethidium bromide induced loss of mitochondrial enzymes. Consequently, the amount of mitochondria, or mitochondrial protein per cell, calculated from the activity of NADH and succinate dehydrogenases has increased nearly 50%. Possible models to explain the control of mitochondrial biogenesis are discussed to explain these results.


Transcriptional control by NF-κB: elongation in focus.
The NF-κB family of transcription factors governs the cellular reaction to a variety of extracellular signals. Following stimulation, NF-κB activates genes involved in inflammation, cell survival, cell cycle, immune cell homeostasis and more. This review focuses on studies of the past decade that uncover the transcription elongation process as a key regulatory stage in the activation pathway of NF-κB. Of interest are studies that point to the elongation phase as central to the selectivity of target gene activation by NF-κB. Particularly, the cascade leading to phosphorylation and acetylation of the NF-κB subunit p65 on serine 276 and lysine 310, respectively, was shown to mediate the recruitment of Brd4 and P-TEFb to many pro-inflammatory target genes, which in turn facilitate elongation and mRNA processing. On the other hand, some anti-inflammatory genes are refractory to this pathway and are dependent on the elongation factor DSIF for efficient elongation and mRNA processing. While these studies have advanced our knowledge of NF-κB transcriptional activity, they have also raised unresolved issues regarding the specific genomic and physiological contexts by which NF-κB utilizes different mechanisms for activation.


Merging Metals and Strained Intermediates.
Strained intermediates such as cyclic alkynes and allenes are most commonly utilized in nucleophilic additions and cycloadditions, but have seen increased use in a third area of reactivity: metal-mediated transformations. The merger of strained intermediates and metal catalysis has enabled rapid access to complex, polycyclic systems. Following a discussion of relevant landmark studies involving metals and strained intermediates, this article highlights recent advances in transition metal-mediated transformations from our laboratory. Specifically, this includes the use of arynes in the synthesis of decorated organometallic complexes, and the utilization of cyclic allenes to access enantioenriched heterocycles. Moreover, the broad applicability of such transformations, and exciting future areas of research are discussed.


A novel endothelial tyrosine kinase cDNA homologous to platelet-derived growth factor receptor cDNA.
Degenerate oligonucleotide primers complementary to the highly conserved subdomains III and VIII of subclass III tyrosine kinase receptors (TKr-III) were utilized to amplify rat aortic cDNA by polymerase chain reaction. Most of the cloned DNA products were rat platelet-derived growth factor receptor beta and macrophage-colony stimulating growth factor receptor cDNAs. Screening of the clones with probes coding for the receptor-specific kinase insert domain allowed the identification of a novel putative TKr-III cDNA, which hybridized with a approximately 6.1 kb mRNA with a distinctive tissue distribution. In situ hybridization on rat tissues and Northern analysis of cultured cells indicate that endothelial cells express a novel putative TKr-III mRNA.


Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.
Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.


Plastid division control: the PDV proteins regulate DRP5B dynamin activity.
Chloroplast division represents a fundamental but complex biological process involving remnants of the ancestral bacterial division machinery and proteins of eukaryotic origin. Moreover, the chloroplast division machinery is divided into stromal and cytosolic sub machineries, which coordinate and control their activities to ensure appropriate division initiation and progression. Dynamin related protein 5B (DRP5B) and plastid division protein 1 and 2 (PDV1 and PDV2) are all plant-derived proteins and represent components of the cytosolic division machinery, where DRP5B is thought to exert constrictional force during division. However, the direct relationship between PDV1, PDV2 and DRP5B, and moreover how DRP5B is regulated during plastid constriction remains unclear. In this study we show that PDV1 and PDV2 can interact with themselves and with each other through their cytosolic domains. We demonstrate that DRP5B interacts with itself and with the cytosolic region of PDV1 and that the two functional isoforms of DRP5B have highly overlapping functions. We further show that DRP5B harbors GTPase activity and moreover that PDV1 and PDV2 inhibits DRP5B-mediated GTP hydrolysis in a ratio dependent manner. Our data suggest that the PDV proteins contribute to the regulation of DRP5B activity thereby enforcing control over the division process during early constriction.


Structural requirements of Na+-dependent antidopaminergic agents: Tropapride, Piquindone, Zetidoline, and Metoclopramide. Comparison with Na+-independent ligands.
Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two pi-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.


Subtle vaginal evisceration resulting in small bowel evisceration: a case report.
Evisceration of bowel contents through the vagina is a rare event that may be complicated by bowel obstruction. We report a case of vaginal evisceration with small bowel obstruction which, in contrast to previous, more dramatic case reports in the literature, is a more subtle and, in fact, characteristic clinical presentation for this unusual occurrence. A 72-year-old woman with a previous history of pelvic surgery presented to the Emergency Department with lower abdominal discomfort and a prolapsing mass from her vagina. She was initially discharged home after bedside reduction of the mass, but returned 48 h later with worsening symptoms. A computed tomography scan on her repeat visit confirmed evisceration of bowel into the vaginal vault with obstruction of distal bowel loops. Surgical and gynecologic services were consulted and the patient underwent partial small bowel resection and vaginal cuff repair in the operating room. Early recognition of subtle presentations of vaginal evisceration is crucial for preserving bowel viability and preventing morbidity from bowel ischemia or infarction. Risk factors for this rare condition include postmenopausal status, previous pelvic surgery, and presence of an enterocele.


A comprehensive analysis of the mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs.
The Omicron variant is spreading rapidly throughout several countries. Thus, we comprehensively analyzed Omicron's mutational landscape and compared mutations with VOC/VOI. We analyzed SNVs throughout the genome, and AA variants (NSP and SP) in VOC/VOI, including Omicron. We generated heat maps to illustrate the AA variants with high mutation prevalence (> 75% frequency) of Omicron, which demonstrated eight mutations with > 90% prevalence in ORF1a and 29 mutations with > 75% prevalence in S-glycoprotein. A scatter plot for Omicron and VOC/VOI's cluster evaluation was computed. We performed a risk analysis of the antibody-binding risk among four mutations (L452, F490, P681, D614) and observed three mutations (L452R, F490S, D614G) destabilized antibody interactions. Our comparative study evaluated the properties of 28 emerging mutations of the S-glycoprotein of Omicron, and the ΔΔG values. Our results showed K417N with minimum and Q954H with maximum ΔΔG value. Furthermore, six important RBD mutations (G339D, S371L, N440K, G446S, T478K, Q498R) were chosen for comprehensive analysis for stabilizing/destabilizing properties and molecular flexibility. The G339D, S371L, N440K, and T478K were noted as stable mutations with 0.019 kcal/mol, 0.127 kcal/mol, 0.064 kcal/mol, and 1.009 kcal/mol. While, G446S and Q498R mutations showed destabilizing results. Simultaneously, among six RBD mutations, G339D, G446S, and Q498R mutations increased the molecular flexibility of S-glycoprotein. This study depicts the comparative mutational pattern of Omicron and other VOC/VOI, which will help researchers to design and deploy novel vaccines and therapeutic antibodies to fight against VOC/VOI, including Omicron.


A Stable Dual-wavelength Thulium-doped Fiber Laser at 1.9 μm Using Photonic Crystal Fiber.
A stable dual-wavelength thulium-doped fiber laser operating at 1.9 μm using a short length of photonic crystal fiber (PCF) has been proposed and demonstrated. The photonics crystal fiber was 10 cm in length and effectively acted as a Mach-Zehnder interferometry element with a free spectral range of 0.2 nm. This dual-wavelength thulium-doped fiber laser operated steadily at room temperature with a 45 dB optical signal-to-noise-ratio.


Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins.
1. During in vitro incubation of liposomes or unilamellar vesicles prepared from egg-yolk or rat-liver phosphatidylcholine with human, monkey or rat plasma the phospholipid becomes associated with a high molecular weight protein-containing component. 2. The phosphatidylcholine . protein complex thus formed co-chromatographs with high-density lipoprotein on Ultrogel AcA34 and has the same immunoelectrophoretic properties as this lipoprotein. 3. Release of the phosphatidylcholine from liposomes was also observed when liposomes were incubated with pure monkey high-density lipoproteins. Under those conditions some transfer of protein from the lipoprotein to the liposomes was observed as well. 4. The observed release of phospholipid from the liposomes is a one-way process, as the specific radioactivity of liposome-associated phosphatidylcholine remained constant during incubation with plasma. 5. It is concluded that either the lipoprotein particle takes up additional phospholipid or that a new complex is formed from protein constituents of the lipoprotein and the liposomal phosphatidylcholine. 6. Massive release of entrapped 125I-labeled albumin from the liposome during incubation with plasma suggests that the observed release of phosphatidylcholine from the liposomes has a highly destructive influence on the liposomal structure. 7. Our results are discussed with special reference to the use of liposomes as intravenous carriers of drugs and enzymes.


Profiling and classification of illicit heroin by ICP-MS analysis of inorganic elements.
Nineteen inorganic elements (Ag, As, Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, P, Pb, Se, Sb, Th, Tl, U, V and Zn) in heroin samples were determined using inductive coupled plasma mass spectrometry (ICP-MS). After Wilcoxon-Mann-Whitney test and correlation analysis, 10 element contents (P, V, Cr, Ni, Cu, Zn, As, Se, Pb, U) and 7 element ratios (U/Ba, Ba/Pb, Cd/Mn, Co/Ni, V/Cr, P/V, Cd/V) were found to be evidently different between heroin samples from "Golden Crescent" and "Golden Triangle". Based on the data set of these 17 variables in 150 authentic heroin samples, classification of origins was successfully achieved utilizing principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). By comparison experiment on 907 unknown samples, the developed discriminant model was proven to be consistent with the widely used organic profiling method, and meanwhile the time consumed per sample was markedly saved, which facilitates high throughput screening in routine analysis.


Design, synthesis, and preliminary evaluation of gabapentin-pregabalin mutual prodrugs in relieving neuropathic pain.
As a part of a program for the development of specific analgesics in relieving neuropathic pain, the purpose of the present study was to investigate a new concept that involves the conjugation of two drugs, gabapentin and pregabalin, as mutual prodrugs using a chemical modification approach. A series of gabapentin-pregabalin diester compounds were synthesized using linear or branch bis-hydroxyl linkers. Their pharmacological properties for treating neuropathic pain were investigated in a rat model of chronic sciatic nerve constriction injury (CCI). In-vivo evaluation demonstrated that 1a and 1b composed of two gabapentin molecules as well as 3a composed of gabapentin and pregabalin with the short linear linker, were effective in reversing tactile allodynia in CCI rats. Compounds with longer or side-branched linkers showed lower efficiencies and severe adverse effects.


A unified theory of nucleation-rate-limited DNA renaturation kinetics.
DNA renaturations under nucleation-rate-limiting conditions on simple DNA such as bacterial and bacteriophage DNA show significant deviation from ideal second-order kinetics when followed by optical density measurements at 260 nm. Ideal second-order kinetics yield linear plots when the data is plotted in the standard reciprocal second-order (RSO) manner. The observed deviations from ideal second-order behavior take the form of steadily downward-curving RSO plots. In this paper, experiments are presented for E. coli and T2 DNA documenting this non-ideal behavior. Since experiments using T4, T5 and B, subtilis DNA yield identical non-ideal behavior, this behavior appears to be a property of DNA renaturation followed by optical density, not a peculiarity of a particular DNA. Identical non-ideal behavior is also seen in kinetics followed by S1 nuclease assay. A theory is developed to explain this deviation from ideal second-order kinetics. The theory also explains why kinetics followed by hydroxyapatite chromatography show nearly ideal second-order kinetics. In contrast to the approach taken by others in developing equations that describe S1 nuclease monitored reactions, our view is that nonideal second-order kinetics are fundamentally due to the reacton of free single strands to yield partially helical duplex species. Later reactions of these species tend to reduce the deviations from non-ideal second-order kinetics.


Context-dependent and seasonal fluctuation in bottlenose dolphin (Tursiops truncatus) vocalizations.
A fundamental question in animal behaviour is the role of vocal communication in the regulation of social interactions in species that organise themselves into social groups. Context dependence and seasonality in vocalizations are present in the communication of many species, although very little research has addressed this dependence in marine mammals. The study presented here examined variations in the rate at which free-ranging dyads of bottlenose dolphins emit social-signals in an effort to better understand the relationship between vocal communication and social context. The results demonstrate that changes in the social-signal production in bottlenose dolphins are related to the sex of the partner, mating season and social affiliation between the components of the dyad. In a context of foraging behaviour on the same feeding ground, mixed (male-female) dyads were found to emit more pulsed burst sounds during the mating season. Another relevant aspect of the study seems to be the greater production of agonistic social-signals in the dyads formed by individuals with a lower degree of social affiliation. Overall, this study confirms a clear relationship between dyad composition and context-specific social-signals that could reflect the motivational state of individuals linked to seasonal changes in vocal behaviour.


ChatGPT in Colorectal Surgery: A Promising Tool or a Passing Fad?
Colorectal surgery is a specialized branch of surgery that involves the diagnosis and treatment of conditions affecting the colon, rectum, and anus. In the recent years, the use of artificial intelligence (AI) has gained considerable interest in various medical specialties, including surgery. Chatbot Generative Pre-Trained Transformer (ChatGPT), an AI-based chatbot developed by OpenAI, has shown great potential in improving the quality of healthcare delivery by providing accurate and timely information to both patients and healthcare professionals. In this paper, we investigate the potential application of ChatGPT in colorectal surgery. We also discuss the potential advantages and challenges associated with the implementation of ChatGPT in the surgical setting. Furthermore, we address the socio-ethical implications of utilizing ChatGPT in healthcare. This includes concerns over patient privacy, liability, and the potential impact on the doctor-patient relationship. Our findings suggest that ChatGPT has the potential to revolutionize the field of colorectal surgery by providing personalized and precise medical information, reducing errors and complications, and improving patient outcomes.


Interferon production in male homosexuals with the acquired immune deficiency syndrome (AIDS) or generalized lymphadenopathy.
We measured serum interferon (IFN) levels and leukocyte IFN production in vitro in homosexual men with AIDS or generalized lymphadenopathy and in asymptomatic homosexual or heterosexual men. Acid-labile interferon alpha was detected in the serum of two patients with AIDS and in three out of nine patients with lymphadenopathy, but not in the sera of healthy homosexual or heterosexual controls. The presence of serum interferon in patients with AIDS or lymphadenopathy was correlated with a marked deficiency of their leukocytes to synthesize interferon alpha in response to viruses or tumor cells, but did not significantly interfere with the production of interferon gamma in response to lectin or bacterial enterotoxin. Our results suggest an inverse correlation between serum interferon alpha and the amount of interferon alpha produced in leukocyte cultures in male homosexuals with AIDS or generalized lymphadenopathy.


Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents.
In order to study the structure-activity relationship (SAR) of C21-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3β-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC50 value of 3.11 μM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C21-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.


Concomitant Vascular War Trauma Saturating a French Forward Surgical Team Deployed to Support the Victims of the Syrian War (2013). Interest of the Vascular Damage Control.
Vascular injuries from war require an emergency treatment whose objective is to quickly obtain hemostasis and the restoration of arterial flow. In this context of heavy trauma and limited means, damage control surgery is recommended and is based on the use of temporary vascular shunts (TVSs). We report the management of the simultaneous arrival of 2 vascular injuries of war in a field hospital. Patient 1 presented a ballistic trauma of the elbow with a section of the humeral artery (Gustillo IIIC). A TVS was set up during the external fixation of the elbow. Final revascularization was carried out and aponevrotomies of the forearm were performed. Patient 2 had a riddled knee with an open fracture of the femur, an avulsion of the popliteal artery, and a hemorrhagic shock. A strategy of damage control surgery was carried out with placing an arterial and venous shunt. Aponevrotomies of the leg were carried out before casting. For the traumatisms of the arteries of the members, the use of shunts is reserved for the lesions of the proximal vessels. Many vascular shunts available have the same performances to restore the arterial flow and prevent secondary thrombosis. The time before the final revascularization depends on the clinical condition of the patient. The value of anticoagulation in these cases was not shown.


Serial transverse enteroplasty and nipple valve construction, two life saving techniques for patients with short bowel syndrome, a report of 5 cases.
Various abdominal pathologies end up with surgical resection of small intestine. When the small intestine remnant is too short for adequate fluid and micronutrients absorption, short bowel syndrome is diagnosed. The disabling condition needs a multidisciplinary approach to design parenteral nutrition, care for thrombotic, hepatic and infectious complications and gradually wean the patient from parenteral nutrition. Various surgical techniques have been introduced to increase absorptive mucosa and enhance the intestinal adaptation process. Serial transverse enteroplasty and nipple valve reconstruction are among the procedures, which will be discussed in the current article. Herein, we presented 5 cases of short bowel syndrome as a consequence of abdominal laparotomies, patients were referred to our center to receive parenteral nutrition and to be prepared for the final autologous gastrointestinal reconstruction or intestinal transplantation, if indicated. Patient's age, performance status and bowel remnant length determines the appropriate technique for autologous gastrointestinal reconstruction. Serial transverse enteroplasty is designed to increase bowel's length by creating zigzag patterns through dilated bowel loops. Presence of ileocecal valve is crucial to delay intestinal transit time and to prevent colonic bacterial transfer to ileum. Patient's with ileocecal valve loss benefit from creating an artificial valve, namely, nipple valve.


Structural analysis and reliability of the Perceived Stress Scale in nursing professionals from Peru.
The objective was to provide psychometric evidence of the 14-item and 10-item version of the Perceived Stress Scale in nursing professionals from Peru. Data on 2848 professionals (92.275% women) between 23 and 69 years old (M = 21.876; SD = 10.763) was extracted from ENSUSALUD 2015. An exploratory structural equation modelling (ESEM) was applied with Mplus 7.0 software to analyse several measurement models in the PSS: unidimensional, bidimensional, models with method factor, and bifactor. Finally, the reliability was analysed. The two-factor structure obtained adequate fit indices, and acceptable factorial loadings (>.50), while the unidimensional model has poor statistical support. The construct and score reliability was also adequate. The two-factor model of the PSS-10 and PSS-14 presents adequate psychometric properties to expand its use to empirical research.


SHANK3 controls maturation of social reward circuits in the VTA.
Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy.


Factors affecting the voluntary intake of food by sheep. 4. The effect of additives representing the primary tastes on sham intakes by oesophageal-fistulated sheep.
1. Sheep with oesophageal fistulas were sham-fed on pelleted lucerne (Medicago sativa) hay to assess the palatability of added chemicals representing the tastes of sweet (sucrose), sour (hydrochloric acid), salt (sodium chloride), bitter (urea) and umami (monosodium glutamate; MSG). 2. Plain pellets and four concentrations of each chemical were sham-fed for 30 min after 5.5 h deprivation in 5 x 5 Latin-square experiments following a period of adaptation feeding. 3. Sucrose, at concentrations of 15-120 g/kg air-dried pellets, depressed intakes with a linear relation between intake (I; g) and concentration (C; g/kg): I = 1001-3.42C. 4. HCl at 6.25-25.0 g/kg pellets had no effect on sham intakes but at 50 g/kg reduced them by 50% of control (P less than 0.05). 5. NaCl at 50 200 g/kg increased sham intakes by 26% (P less than 0.01) with no evidence of a dose-related effect. 6. Urea at 10-80 g/kg decreased sham intakes by 26.9% (P less than 0.01) with no evidence of a dose-related effect. 7. MSG at 5-40 g/kg in two experiments increased sham intakes by 16.1 and 40.8% (P less than 0.05). In another experiment at 1-8 g/kg there was no significant effect. 8. When palatability and post-ingestive effects are separated by sham-feeding, the effect of added chemicals on intake may be completely different from when they are ingested normally (e.g. NaCl and sucrose). This newly developed technique enables the palatability effect of feed additives to be tested critically and economically.


Recent burns of the hand. Early excision-graft versus conventional treatment. A retrospective study during two years.
Early excision-graft of burned hands seems to have totally superseded the conventional method of progressive detorsion often with late grafting. Does this treatment merit acceptance under these conditions? Do the theoretical advantages of aggressive methods counter-balance the primary difficulty of diagnosing the initial depth of burn? Are these fewer difficulties and risks in early excision-graft than in the slower methods? Can we ascribe the failure of conventional method to a poor technical realisation? Following a short summary of the principles of the two methods, we attempt to answer these questions by a retrospective study comparing identical series of patients. We have begun a prospective randomized trial and present the preliminary results here.


Independence between the amount and structure of variability at low force levels.
The purpose of the current experiment was to investigate the amount (standard deviation (S.D.) and coefficient of variation (CV)) and structure (approximate entropy (ApEn)) of force variability at very low force levels. Participants produced isometric force output of index finger abduction at five levels (0.4, 0.8, 1.0, 2.0, and 4.0 N) with high and low visual feedback gain. The findings showed that: subjects scaled their force output to the targets; S.D. increased non-linearly with force level and decreased with visual gain; and CV decreased with force level as well as visual gain. ApEn of the force output did not change as a function of force level, although the high gain increased ApEn in contrast to low gain. It is proposed that the recruitment of additional motor units at very low force levels does not significantly alter the structure of the force output, although it does increase the magnitude of force and its amount of variability. Overall, the findings provide evidence that the amount and structure of motor variability can be influenced by separate control processes at low force levels.


The value of diastolic flow reversal in the descending thoracic aorta as a determinant of invasively measured aortic pulse pressure.
Although the diastolic flow reversal of the descending aorta has been recognized in patients with aortic regurgitation, its generation without this condition is still unknown. This study was performed to investigate whether flow patterns of the descending thoracic aorta, as measured by echocardiography, can represent invasively measured aortic pulse pressure (APP). A total of 100 patients (age, 62.3±11.0 years; men, 62.0%) undergoing invasive coronary angiography (ICA) was analyzed. APP was measured at ascending thoracic aorta using pigtail catheter before ICA. Flow in the descending thoracic aorta was assessed using pulse wave Doppler echocardiography, and R/F ratio was defined as reverse peak velocity (R)/forward peak velocity (F). Eighty patients (80.0%) had obstructive coronary artery disease (CAD) (≥50% stenosis of one or more epicardial coronary arteries) in ICA. APP and R/F ratio were significantly higher in patients with obstructive CAD than those without (P<.05 for each). Both R/F ratio (β=0.379, P<.001) and APP (β=0.255, P<.001) were positively correlated with age. In simple linear regression analysis, there was a significant positive correlation between R/F ratio and APP (β=0.266, P<.001). This correlation remained significant even after controlling for potential confounders including age, gender, E/e', and left atrial volume index in multiple linear regression analysis (β=0.193, P=.036). R/F ratio may be independently associated with APP in patients undergoing ICA.


Discovery of new long noncoding RNAs associated with ulcerative colitis with a novel general microarray expression data.
UC is a chronic, nonspecific disease and characterized by a chronic relapsing intestinal inflammation, which puts a person at a higher risk of developing bowel cancer, while the causes of UC are unknown. Recently, with the development of microarray technology, more and more studies are focusing on the potential roles of long noncoding RNAs (lncRNAs) in the pathogenesis of diseases. The purpose of this study is to devise a method, based on cDNA microarray probe genomics data, to computationally determine the potential function of evolutionary conserved lncRNAs in ulcerative colitis (UC). We analysed a total of 12,593 microarray probes present in the Ensembl, OMIM, UniGene, and Gene Ontology databases. We found that lncRNA n385775 was significantly higher (P < 0.001) in patients with active UC, while n336281 (P = 0.017), n341081 (P = 0.041), and n387236 (P = 0.006) were significantly lower. Then, we validated our findings by measuring the expression of lncRNAs in colon tissue samples from patients affected by UC. Moreover, we validated the expression pattern of the lncRNAs in two cell lines, Caco2/bbe and T84, treated with TNF-α. In Caco2/bbe cells, lncRNA n385775 was significantly upregulated after TNF-α treatment (P = 0.002). This study reports a novel method to re- annotate the transcriptome expression profile from existing cDNA microarray data as a potential approach to investigate the function of lncRNAs in UC.


The Health-Grant University: a comprehensive national health education plan.
Although the need for universal and better health education has been recognized, no nationwide comprehensive program has been established. Consequently, we are proposing founding a national program of statewide health education networks, comparable in some ways to the Cooperative Extension Services of Land-Grant and Sea-Grant Universities. One institution in each state would qualify for designation as the State Health-Grant University, and all other public and private colleges located throughout the state would be encouraged to appoint one faculty member to serve as the health educator for the corresponding service area. Each health educator would receive an adjunct appointment at the health-grant university and would be required to participate in special training sessions and to master progressive health education strategies. The health educator would link the academic world and the community, educating the community about health and disease prevention and the significance of lifestyle. By catalyzing and coordinating efforts with teachers, ministers, nurses, physicians, business leaders, and others, the health educator would make an important contribution to the community. By addressing disease prevention and health maintenance, the Health-Grant University Program would strive to motivate the community to achieve greater individual health initiatives, while helping develop skills for personal health management and providing access to needed health services. Federal legislation would be required to create a national commission to coordinate the program, but community volunteers would make the program cost-effective and self-sustaining.


Atrophins' emerging roles in development and neurodegenerative disease.
The Atrophins are a widely expressed family of transcriptional co-regulators found in all metazoans. Atrophin1 was first identified as a neurodegenerative disease gene whereas Atrophin2 was identified based on homology. Phylogenetic studies indicate that the primordial Atrophin was an Atrophin2 type of gene and Atrophin2 has critical functions in normal mouse embryonic development whereas Atrophin1 is dispensable. Atrophins can interact with a wide range of proteins including membrane receptors, nuclear hormone receptors and other DNA binding transcription factors and can shuttle between the cytoplasm and the nucleus. In the nucleus, Atrophins can act as either co-repressors or co-activators and taken together this suggests that they are intermediaries in transcriptional responses to a diverse array of exogenous signals. Despite progress in understanding the normal role of Atrophins, the mechanism whereby mutations in Atrophin1 cause neurodegeneration has remained enigmatic, although most studies have focused on the idea that neurodegeneration is related to inappropriate transcriptional repression.


Transitional changes in cardiac and cerebral hemodynamics in term neonates at birth.
To describe cardiac function, cerebral regional oxygen saturation (rSO(2)), and cerebral blood flow (CBF) that correspond to changes in arterial oxygen saturation (SaO(2)) in normal term neonates immediately after birth and after the transition. In this prospective observational study, cardiac function and cerebral hemodynamics were assessed by echocardiography and Doppler ultrasonography 3 times during the first 20 minutes after vaginal delivery, then again at 24-48 hours after delivery. Cerebral rSO(2) (by near-infrared spectroscopy) and preductal SaO(2) (by pulse oximetry) were assessed continuously. In 20 neonates, SaO(2) increased progressively from 65% at 1 minute after birth to 97% at 17 minutes after birth. Cerebral rSO(2) increased from 47% at 1 minute to 83% at 8 minutes, then decreased progressively to 73% at 20 minutes. Middle cerebral artery mean velocity decreased from 34 cm/s at 7 minutes to 25 cm/s at 14 minutes. The patent ductus arteriosus (PDA) shunt was balanced at 5 minutes but became increasingly left to right. Left ventricular stroke volume was increased. Middle cerebral artery mean velocity demonstrated an inverse relationship with the PDA shunt. Further hemodynamic changes were noted on the posttransitional assessment. After birth, ductal shunting rapidly changes from balanced to left to right, with a responsive increase in left ventricular stroke volume. Cerebral rSO(2) increases as SaO(2) rises during the first 8 minutes, subsequently, it decreases due to a drop in CBF and despite a further increase in SaO(2). The reduction in CBF is likely due to an increase in arterial O(2) content, PDA shunting, or both.


The effectiveness of "Protex" for disinfection of the ultrasound probe.
The aim of this study was to evaluate the effectiveness of "Protex" (Parker; Fairfield, NJ, USA) for disinfection of ultrasound probes. We examined bacterial contamination on ultrasound probes that were wiped with a plain paper towel, with a plain and an ethanol-soaked paper towel, or with a plain and Protex-soaked paper towel. The plain paper towel was used to remove the gel, and was contaminated by large numbers of bacteria, but the use of ethanol-soaked paper towels and that of paper towels soaked in Protex™ broad-spectrum disinfectant (Parker: Fairfield, NJ, USA) reduced those numbers markedly.


Incidental findings of thyroid tissue in cervical lymph nodes: old controversy not yet resolved?
The clinical significance of papillary or follicular thyroid tissue incidentally discovered in cervical lymph nodes during pathological assessment of neck dissections for non-thyroid cancers of the upper aero-digestive tract is critically reviewed. Special emphasis is given to controversies over normal-looking, nodal, thyroid follicles. Arguments for and against the benign nature of these follicles are considered together with processes that could be involved in their formation. The admittedly limited evidence suggests that benign, thyroid follicular inclusions rarely occur in cervical lymph nodes. Histological criteria that could be helpful in recognizing the inclusions, which include assessing their extent in conjunction with the size of the node, are discussed. Finally, an algorithm based on collaboration between specialists, correlating histological findings with imaging and loco-regional control of the upper aero-digestive tract cancer, is suggested for the management of patients with incidentally discovered, nodal thyroid tissue.


Opioid-mediated acute responses to alcohol: ethanol potentiates opioid actions on the guinea pig ileum.
Acute administration of ethanol can potentiate the inhibitory effects of exogenously administered opioids on release of acetylcholine from the guinea pig's enteric nervous system. Ethanol also appears to inhibit the release of enteric substance P by enhancing the inhibitory action of simultaneously released endogenous opioids. One consequence of this mechanism of action is that those states that result in the activation of opioid-containing systems, such as stress, might also be the conditions under which the opioid component of the actions of ethanol are the most pronounced.


Preliminary hazard assessment of polychlorinated biphenyls, polybrominated diphenyl ethers, and polychlorinated dibenzo-p-dioxins and dibenzofurans to Yangtze finless porpoise in Dongting Lake, China.
Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), a protected endangered species, is the sole freshwater subspecies of finless porpoise, living only in the middle and lower reaches of the Yangtze River, China, and its appended lakes. Its population has decreased sharply to 1,400 because of human activities, including environmental contamination. In the present study, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined in the blubber, liver, kidney, stomach, small intestine, and brains of five individual Yangtze finless porpoises collected from 1998 to 2004. The results showed PCB concentrations ranged from 0.06 to 1.89 microg/g lipid weight in the organs and consisted mainly of penta-, hexa-, and decachlorinated biphenyls. The PBDE concentrations were between 5.32 and 72.76 ng/g lipid weight. Tetra-, penta-, and hexabrominated diphenyl ethers were the major homologues. The PCDD/F concentrations ranged from 65 to 1,563 pg/g lipid weight, and their predominant homologues were penta- and hexachlorinated dibenzofurans and hepta- and octachlorinated dibenzo-p-dioxins. The hazard quotients (HQs) based on toxic equivalency were determined to be greater than one in all individuals for PCBs, for PCDD/Fs, and for PCBs and PCDD/Fs In addition, HQs would be higher if PBDEs were included. The results suggest that reduction of environmental contamination may contribute greatly to protecting this highly endangered species.


General immunological status of nasopharyngeal carcinoma patients in Singapore.
Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole.


Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone.
To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps. No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC0-infinity) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng.h/L after the thalidomide regimen (paired t test, P > .05). The values for norethindrone were 103 +/- 54 micrograms.h/L and 107 +/- 58 micrograms.h/L (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC0-infinity 41.1 +/- 13.9 micrograms.h/mL; day 21 AUC0-infinity 59.6 +/- 27.3 micrograms.h/mL (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%. The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.


Hazard report. Loose mounting screws on Cardinal Health Avea ventilator cart may cause cart to tip or collapse.
If the four mounting screws that connect the support column to the base of certain older Avea ventilator carts loosen, the cart may tip over as a result. The supplier's technical bulletin about this problem was not received by all users. Facilities with affected units should inspect the carts to verify that a thread-locking compound has been applied to the mounting screws, as recommended by the supplier.


Automated hollow-fiber liquid-phase microextraction coupled with liquid chromatography/tandem mass spectrometry for the analysis of aflatoxin M₁ in milk.
An automated hollow fiber liquid-phase microextraction (HF-LPME) coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for the extraction and determination of aflatoxin M1 (AFM1) in milk samples. Parameters affecting the extraction efficiency, such as the extraction phase, matrix conditions, extraction time and temperature, were investigated. Under the optimal conditions (ratio of water to milk, 4:1; extraction time, 50 min; extraction temperature, 50°C; extraction phase, 50 mg L(-1) anti-AFM1 antibody in PBS buffer solution; volume of HCl solution, 250 μL; agitation speed, 250 rpm), the matrix-matched calibration curve for AFM1 determination showed good linearity in the range of 0.25-5 μg kg(-1). The enrichment factor (EF) reached 48, and the limits of detection and quantification were 0.06 and 0.21 μg kg(-1), respectively. The developed method was successfully applied for the extraction of AFM1 from spiked milk samples, with recoveries from 61.0% to 106.7%. The method was highly specific to AFM1 analysis, and the results demonstrated that the method can be automated, inexpensive, and free from interference.