Molecular and Phenotypic Characterization of Nine Patients with STAT1 GOF Mutations in China.
Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.


Double-blind placebo-controlled trial of intranasal IgE pentapeptide.
The safety and efficacy of intranasal HEPP (IgE pentapeptide) was evaluated in 30 patients with IgE-mediated allergic rhinitis. Statistically and clinically significant differences were observed in the degree of clinical improvement between HEPP and placebo groups. IgE pentapeptide 0.5% intranasal solution appears to be safe and effective in the treatment of allergic rhinitis.


Competitive Immunoassays Using Antigen Microarrays.
In this work, a non-fouling antigen competitive immunoassay microarray based on the polymer brush is reported to detect multiple mycotoxins. The detection is achieved by utilizing highly specific monoclonal antibodies produced in our laboratory. The polymer brush, poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA), is synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP) on standard glass slides. In the polymer brush, the epoxy groups of glycidyl methacrylate (GMA) residues provide covalent binding sites for spotted antigens. Moreover, the abundant poly(ethylene glycol) (PEG) side chains in the brush are able to ultimately suppress the nonspecific protein adsorption in solution (non-fouling). The polymer brush shows a high and uniform protein loading, along with a high resistance to nonspecific protein absorption that are both important to achieve a highly sensitive immunoassay. As a demonstration of a multiplex assay, aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN) are selected as antigen targets for simultaneous detections using the microarray.


Carl Gussenbauer and the first artificial larynx after total laryngectomy.
The aim of this historical vignette is to delve into the description and use of the first artificial larynx, developed by Carl Gussenbauer, and used after Theodor Billroth's first total laryngectomy, performed on December 31, 1873.


Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer.
Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.


The lithospheric-to-lower-mantle carbon cycle recorded in superdeep diamonds.
The transport of carbon into Earth's mantle is a critical pathway in Earth's carbon cycle, affecting both the climate and the redox conditions of the surface and mantle. The largest unconstrained variables in this cycle are the depths to which carbon in sediments and altered oceanic crust can be subducted and the relative contributions of these reservoirs to the sequestration of carbon in the deep mantle1. Mineral inclusions in sublithospheric, or 'superdeep', diamonds (derived from depths greater than 250 kilometres) can be used to constrain these variables. Here we present oxygen isotope measurements of mineral inclusions within diamonds from Kankan, Guinea that are derived from depths extending from the lithosphere to the lower mantle (greater than 660 kilometres). These data, combined with the carbon and nitrogen isotope contents of the diamonds, indicate that carbonated igneous oceanic crust, not sediment, is the primary carbon-bearing reservoir in slabs subducted to deep-lithospheric and transition-zone depths (less than 660 kilometres). Within this depth regime, sublithospheric inclusions are distinctly enriched in 18O relative to eclogitic lithospheric inclusions derived from crustal protoliths. The increased 18O content of these sublithospheric inclusions results from their crystallization from melts of carbonate-rich subducted oceanic crust. In contrast, lower-mantle mineral inclusions and their host diamonds (deeper than 660 kilometres) have a narrow range of isotopic values that are typical of mantle that has experienced little or no crustal interaction. Because carbon is hosted in metals, rather than in diamond, in the reduced, volatile-poor lower mantle2, carbon must be mobilized and concentrated to form lower-mantle diamonds. Our data support a model in which the hydration of the uppermost lower mantle by subducted oceanic lithosphere destabilizes carbon-bearing metals to form diamond, without disturbing the ambient-mantle stable-isotope signatures. This transition from carbonate slab melting in the transition zone to slab dehydration in the lower mantle supports a lower-mantle barrier for carbon subduction.


Augmented and virtual reality in spine surgery.
Augmented Reality (AR) and Virtual Reality (VR) have developed unprecedentedly in recent years, providing interesting opportunities for medical applications. Their integration into clinical assessment, surgical workflow, and training has shown tremendous potential to improve daily life activity in spine surgery. The paper explores the utilization of VR and AR in spine surgery, with their applications, benefits, challenges, and forthcoming prospects.


The laboratory identification of serum rheumatoid factor in the dog.
A modified Rose-Waaler test with sheep red blood cells coated with canine IgG was found satisfactory for detecting rheumatoid (antiglobulin) factor (RF) in dog serum. Low titres of RF were found in some normal dogs. Most dogs with rheumatoid arthritis were positive for RF at titres of 1 in 40 or greater. A small proportion of dogs with diseases other than polyarthritis were also positive for RF. A commercial slide agglutination test used for detecting human RF was unsatisfactory for the dog, giving false positive and negative reactions. A latex tube agglutination test with latex particles coated with dog IgG was developed but non-specific agglutination was a constant technical problem.


Ezrin expression in rectal cancer predicts time to development of local recurrence.
Improved outcome after rectal cancer surgery requires identification of novel risk factors of tumour recurrence in order to personalise therapy, that is, enhanced selection of high-risk patients to additional radiochemotherapy or intensified follow-up. In several tumour types, including colorectal cancer, high expression of the membrane-cytoskeleton linker ezrin has been suggested to impair prognosis but has not yet reached clinical application. We evaluated the expression of ezrin in rectal cancer with a focus on the identification of a marker for local tumour recurrence. Immunohistochemical expression of ezrin was analysed in 104 primary rectal cancers from patients who developed local recurrences despite being treated with R0 major abdominal surgery. Time to local recurrence and distant metastasis as well as 5-year overall and cancer-specific survival were used as end points. Ezrin expression was weak in 17% of the tumours, moderate in 62%, and intense in 21%. The time to local recurrence was significantly shorter (p = 0.0004) for patients with tumours showing high ezrin expression. No correlation between ezrin expression and time to distant metastasis was identified. Survival data were similar between groups irrespective of ezrin expression in the primary tumours. Our findings suggest that increased expression of ezrin may represent a marker of aggressive biological behaviour in rectal cancer. Although further validation is needed, ezrin may represent a relevant marker for personalised treatment of rectal cancer with respect to risk of local recurrence after R0 surgery.


Responses of cowpeas (Vigna unguiculata (L.) Walp.) to progressive soil drought.
Greenhouse-grown cowpeas, Vigna unguiculata (L.) Walp., were subjected either to well-watered or to progressive soil drought conditions between 10-40 days after emergence. Stomatal closure was found to correlate with the progressive drying of soil while leaf water potentials were not very different from the well-watered plants. Reduction in leaf turgor resulted in a reduced rate of leaf extension but increased that of root. Stomatal conductance and transpiration rates of soil-drought plants were similar to well-watered plants in the morning, but were greatly reduced in the afternoon till evening. It is suggested that the maintenance of transpiration rates per unit leaf area of soil-drought cowpeas in the morning is due to the reduction in the leaf area per plant and possibly the hydration of the plants in the night through enhanced root growth.


Developmental aspects of dichoptic viewing.
Age-related performance changes on a dichoptic viewing task were examined with twenty-five (25) individuals in a cross-sectional design. Using a double-report procedure, subjects were asked to identify two different consonant-vowel graphemes presented separately to the same foveal area of each eye (i.e., dichoptic stimulation). Stimuli were presented at stimulus-onset asynchronies (SOAs) ranging from 0 to 300 msec in 50-msec steps. Results indicated that the number of both-correct trials (i.e., correct reports of both stimuli in a dichoptic pair) significantly increased with age, while single-correct trials (a correct report of only one stimulus in the pair) significantly decreased with age. In addition, the shape of the masking functions indicated lagging stimuli were reported more accurately than leading stimuli at SOAs of 50-300 msec for all subjects. Younger subjects exhibited peak masking effects for synchronous presentations (0-msec SOA) while older individuals showed peak masking at SOAs of 50 msec. Results suggest developmental performance changes noted in processing visual information parallel, to a remarkable degree, those observed in processing auditory information.


Elemental composition, morphology and mechanical properties of calcified deposits obtained from abdominal aortic aneurysms.
Calcified deposits exist in almost all abdominal aortic aneurysms (AAAs). The significant difference in stiffness between these hard deposits and the compliant arterial wall may result in local stress concentrations and increase the risk of aneurysm rupture. Calcium deposits may also complicate AAA repair by hindering the attachment of a graft or stent-graft to the arterial wall or cause vessel wall injury at the site of balloon dilation or vascular clamp placement. Knowledge of the composition and properties of calcified deposits helps in understanding the risks associated with their presence. This work presents results of elemental composition, microscopic morphology, and mechanical property measurements of human calcified deposits obtained from within AAAs. The elemental analyses indicate the deposits are composed primarily of calcium phosphate with other assorted constituents. Microscopy investigations show a variety of microstructures within the deposits. The mechanical property measurements indicate an average elastic modulus in the range of cortical bone and an average hardness similar to nickel and iron.


Acute Cholecystitis Complicated with Portal Vein Thrombosis: A Case Report and Literature Review.
Portal vein thrombosis (PVT) is an infrequent clinical condition usually associated with multiple etiological factors and diseases. In some cases, PVT remains undiagnosed and is incidentally detected during routine examination for a known etiology. Here, we present a rare case of portal vein thrombosis associated with acute cholecystitis in a 31-year-old man. Conservative treatment may be a feasible and safe approach for the management of PVT with acute cholecystitis, if treated at an early stage. Moreover, initial diagnosis based on radiological evaluation is possible only if the surgeons are familiar with this unusual condition. Therefore, a high index of suspicion is required for early diagnosis and management of patients with acute cholecystitis-associated PVT.


Inter-relationships between burnout, personality and coping features in residents within an ACGME-I Accredited Psychiatry Residency Program.
Burnout during residency training is associated with various factors. Within the context of stress/coping transactional model in which one's personality can influence stress appraisal and coping, there is limited evidence examining the relationship between burnout and personality factors amongst psychiatry residents. We aim to evaluate the prevalence of burnout within a cohort of psychiatry residents and its relationship with personality factors, demographic, work-related factors and coping features. We conducted a cross-sectional study involving 50 out of 77 eligible residents (response rate 64.9%) and administered the Oldenberg Burnout Inventory (OLBI), NEO-Five Factor Inventory (NEO-FFI) and Brief COPE Inventory. Burnout was defined as crossing the thresholds for exhaustion (≥2.25) and disengagement (≥2.1) scores. We compared the burnout vs nonburnout groups and examined the relationship between burnout, personality factors and coping strategies using correlational and mediational analyses. Overall, 78% of our cohort met criteria for burnout. Burnout was correlated with hours of work per week (rs = .409, P = .008), neuroticism (OR 1.2, 95% CI 1.01-1.43, P = .041) and avoidance coping (OR 1.61, 95% CI 1.06-2.46, P = .025). Neuroticism was significantly correlated (all P < .001) with all coping domains (Seeking Social Support, rs = 0.40; Problem Solving, rs = 0.52; Avoidance, rs = 0.55; Positive thinking, rs = 0.41) and was a partial mediator between avoidance coping and burnout (β of indirect path = 0.168, [SE = 0.066]; P = .011). We found a considerable burnout rate amongst psychiatry residents which was associated with neuroticism and avoidance coping, and suggest ways to better tackle occupational burnout during residency training.


Erratum: KLF4 suppresses the migration of hepatocellular carcinoma by transcriptionally upregulating monoglyceride lipase.
[This corrects the article on p. 1019 in vol. 8, PMID: 30034939.].


Analysis of the burden and trend of injury in Sichuan, China, from 2006 to 2015: results from the national injury surveillance system.
This study investigates the distribution, burden and trends of injuries in Sichuan, China. A surveillance study using injury data collected by the National Injury Surveillance System. 312 511 injury cases reported in the National Injury Surveillance System in Sichuan, China, from 2006 to 2015. Years of potential life lost (YPLL) were calculated to determine the disease burden from injuries. Trend analysis was performed to assess the trends in specific injuries over time. A total of 312 511 injury cases were reported in the last 10 years in Sichuan with 192 904 (men: 58.58%) and 119 607 (men: 67.11%) cases from the urban and rural surveillance hospitals, respectively. The annual number of injury cases increased from 21 257 in 2006 to 44 112 in 2015 with an average annual increase of 8.45%. The top three common causes of injury were fall (29.3%), animal-related injury (19.1%) and road-related injury (14.6%) in the urban area and fall (38.4%), road-related injury (17.2%) and blunt injuries (16.0%) in the rural area. YPLLs from injuries accounted for 13% of the total YPLLs in the urban area. The number of injury cases varied according to rural/urban areas and gender and increased sharply in Sichuan over the last decade. It is necessary to develop targeted prevention and control measures to reduce the disease burden of injuries.


Diagnostic specificity of sensory and motor nerve conduction variables in early detection of carpal tunnel syndrome.
In the carpal tunnel syndrome (CTS) sensory nerve conduction is more sensitive than motor conduction. However, 8%-25% of the sensory distal latencies in symptomatic hands may still be normal. A systematic study was made of the median, ulnar and radial orthodromic nerve conduction velocities (SNCV) stimulating each of the fingers separately. Four SNCVs from the median nerve, two SNCVs from the ulnar nerve and one from the radial nerve were obtained, and the ratio of the median to radial SNCV and the ratios of the median and ulnar SNCVs were estimated. The significance of these parameters in the diagnosis of the CTS was studied, and a rapid technique for the screening of nerve entrapment in the initial stages of the disease is proposed. Three hundred and seventy-five symptomatic hands were examined. Seventy-five hands showed normal distal latency, in which cases, however, the SNCV of the ring finger was always outside the normal range, while the SNCVs of the thumb, index and middle fingers were abnormal in 64%, 80% and 92% of cases respectively. The amplitudes of the sensory responses were the least sensitive of the parameters studied. Our results suggest that a study of the median nerve digital branch to the ring finger may be of value in providing an easily performed and rapid technique for screening an early median nerve entrapment at the wrist.


Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.
Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.


Metastatic cervical carcinoma presenting as psoas abscess and osteoblastic and lytic bony metastases.
A 60-year-old Chinese lady presented with a left flank mass and weight loss. Plain films showed a sclerotic L1 vertebral body, osteopenic L2 and L3 vertebral bodies and loss of left psoas outline. However initially unrevealed history of previous carcinoma of the cervix caused confusion as to the aetiology of a sclerotic vertebral body associated with an left flank collection. Psoas abscess with adjacent bony osteomyelitis was initially suspected. The left flank mass turned out to be an infected necrotic large metastatic lymph node compressing the lower pole of the left kidney. The sclerotic and osteopenic vertebral bodies represented an unusual presentation of bony cervical carcinoma metastases.


Risk factors for nodal micrometastasis of submucosal gastric carcinoma: assessment of indications for endoscopic treatment.
BACKGROUND: Despite the widespread use of endoscopic mucosal resection (EMR) for intramucosal gastric carcinoma, there is no standardized therapy for those patients in whom the carcinoma is found, after EMR, to have invaded the submucosa.Our aim in this study was to examine the relationship between the clinicopathological features of submucosal invasive carcinomas and their incidence of nodal micrometastasis, as detected by anti-human cytokeratin immunohistochemistry, in order to assess the curative potential of submucosal carcinoma by EMR.METHODS: Fifty surgically resected submucosal gastric carcinomas which would have satisfied the absolute indications for EMR, except for the criterion of submucosal invasion, were examined. The extent of submucosal invasion was determined by measuring its vertical and horizontal spread. Immunohistochemical analysis was performed with anti-human cytokeratin antibody (CAM5.2).RESULTS: Three of 50 cases (6.0%) were positive for nodal metastasis by routine H&E examination. Nodal micrometastases were detected in 11 of 47 cases (23.4%). Statistical analysis revealed that both the depth and the width of carcinoma in the submucosa were significantly larger in cases with than in those without micrometastasis ( P = 0.019 and P = 0.006, respectively). The group with lymphatic invasion showed more frequent micrometastasis than the group without ( P = 0.014). There were no micrometastases in submucosal carcinomas whose submucosal invasion was less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally.CONCLUSIONS: The present study indicates that differentiated gastric adenocarcinoma with minimal submucosal invasion (less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally) and not accompanied by peptic ulcer or other risk factors, such as lymphatic invasion, can be considered as having high curative potential by EMR alone, without the necessity for further radical surgery.


Novel gene Merlot inhibits differentiation and promotes apoptosis of osteoclasts.
Extended osteoclast longevity is deeply involved in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis, though the mechanisms that determine osteoclast lifespan are not fully understood. Here we present findings indicating that the newly characterized gene Merlot, which encodes a highly conserved yet uncharacterized protein in vertebrates, is an important regulator for termination of osteoclastogenesis via induction of apoptosis. Mice lacking Merlot exhibited low bone mass due to increased osteoclast and bone resorption. Furthermore, osteoclast precursors overexpressing Merlot failed to differentiate into mature osteoclasts, while Merlot deficiency led to hyper-nucleation and prolonged survival of osteoclasts, accompanied by sustained nuclear localization of nuclear factor of activated T cell c1 (NFATc1) and derepression of glycogen synthase kinase-3β (GSK3β) activity, known to regulate NFATc1 activity and induce apoptosis. Merlot-deficient osteoclasts were found to represent suppression of caspase-3-mediated apoptosis and Merlot deficiency caused transcriptional downregulation of a proapoptotic cascade, including Bax, Bak, Noxa, and Bim, as well as the executor caspase members Casp-3, -6, and -7, and upregulation of anti-apoptotic Bcl2, resulting in a low apoptotic threshold. Thus, Merlot regulates osteoclast lifespan by inhibition of differentiation and simultaneous induction of apoptosis via regulation of the NFATc1-GSK3β axis.


Structure of myosin/paramyosin filaments from a molluscan smooth muscle.
Small-angle X-ray diffraction patterns of chemically skinned pedal retractor muscles from Mytilus (PRM) in the relaxed state show a set of diffuse off-meridional reflections that arise from a helical array of myosin crossbridges with 8/3 screw symmetry. Experiments involving extraction of myosin as well as analysis of the rigor pattern have been used to confirm the origin of these reflections. The relatively high myosin/paramyosin molar ratio (1.3 to 1.6) in PRM compared to other molluscan smooth muscles may account for the observation of the relatively stronger diffraction from the myosin array. Thick filaments isolated from PRM and contrasted by negative staining for electron microscopy appear to be very long (up to 17 micron), and to have a rather small diameter (about 40 nm at the center); they taper gradually toward the ends. These filaments show a clear transverse band pattern repeating at 14.4 nm and elongated projections (crossbridges) at the surface except in the central bare zone. Optical diffraction patterns show reflections from crossbridges consistent with the X-ray patterns of the relaxed whole muscle. Filaments unidirectionally shadowed with platinum show diagonal striations running at an angle of about 17 degrees to the filament axis, revealing that the crossbridges are arrayed in a right-handed helix. The paramyosin core is clearly seen upon extraction of myosin. Observations on both negatively stained and sectioned material are consistent with the results of Elliott (1979) and Bennett & Elliott (1981) suggesting a layered structure of the core. Cores stripped of myosin, however, appear to undergo some distortion indicating that the three-dimensional structure is not yet completely solved. The assembly of these thick filaments presents intriguing structural problems since the myosin surface lattice does not appear to have the same symmetry as the underlying paramyosin core.


Still wanted: a reproducible demonstration of a genuine C1 attention effect.
Slotnick (this issue) has specified a number of experimental parameters that appear critical for enabling an attention-related modulation of the C1 component. These include stimulus presentation in the upper visual field, the presence of distractors, a high perceptual or attentional load, and measurements at midline occipito-parietal sites. While we agree with many of these recommendations, we would modify others and even dispute a few. Despite the employment of these parameters in a few existing studies, there has not yet been a convincing, reproducible demonstration of a modulation of the C1 component by spatial attention that can be localized to primary visual cortex.


Experimental confirmation of Serratia marcescens contamination in multiple-dose vials of heparin-saline solution.
The initial contamination of heparin-saline solution (HS) in multiple-dose vials (MDVs) by Serratia marcescens was experimentally investigated using various isolates. Isolates I2 and S1 were from blood specimens from patients with a hospital-acquired infection (HAI). Isolates I13 and FHSM9043 were from urine and blood specimens, respectively, from patients without HAI. Isolate I124, with a pulsed-field get electrophoresis pattern identical to that of isolate I2, was from the hospital environment. Viable cells of isolate I2 were carried over into the HS of MDVs when the contaminated rubber septum was pierced with a syringe needle. When the outside surface of the septum was contaminated by inoculating it with wet-cell suspensions in HS or Müller-Hinton broth, the viable cells carried over were detected at a minimum inoculum size (MIS) of 10(3) s cfu/ml. However, when the surface was contaminated by inoculating it with dry-cell suspensions, the viable cells carried over were detected at an MIS of 10(7) s cfu/ml. The viable cells in the internal lumen of the needle much more than those on its outside surface spread to the HS of MDVs. For exposures of 24 h and 72 h at 4 degrees C to HS with 1% benzyl alcohol as a preservative in MDVs, viable cells of all isolates tested were detected at MIS values of 1 s and 10 s cfu/ml, respectively, increases three orders of magnitude smaller than those of reference strain IFO3736. These results suggest that S. marcescens isolates are readily carried over into the HS of MDVs by piercing a wet, contaminated rubber septum with a syringe needle. Also, despite the sterilization action of 1% benzyl alcohol, the organism persistently survived at 4 degrees C, even when initial contamination was with a small amount of inoculum.


Differential mechanism of the effects of ester-type local anesthetics on sarcoplasmic reticulum Ca-ATPase.
The effect of the local anesthetics procaine and tetracaine on sarcoplasmic reticulum membranes isolated from two masticatory muscles, masseter and medial pterygoid, was tested and compared to fast-twitch muscles. The effects of the anesthetics on Ca-ATPase activity, calcium binding, uptake, and phosphorylation of the enzyme by inorganic phosphate (Pi) were tested with radioisotopic methods. Calcium binding to the Ca-ATPase was non-competitively inhibited, and the enzymatic activity decreased in a concentration-dependent manner. The inhibition of the activity depended on pH, calcium concentration, the presence of the calcium ionophore calcimycin, and the membrane protein concentration. Unlike fast-twitch membranes, the pre-exposure of the masseter and medial pterygoid membranes to the anesthetics enhanced the enzymatic activity in the absence of calcimycin, supporting their permeabilizing effect. Procaine and tetracaine also interfered with the calcium transport capability, decreasing the maximal uptake without modification of the calcium affinity for the ATPase. Besides, the anesthetics inhibited the phosphorylation of the enzyme by Pi in a competitive manner. Tetracaine revealed a higher inhibitory potency on Ca-ATPase compared to procaine, and the inhibitory concentrations were lower than usual clinical doses. It is concluded that procaine and tetracaine not only affect key steps of the Ca-ATPase enzymatic cycle but also exert an indirect effect on membrane permeability to calcium and suggest that the consequent myoplasmic calcium increase induced by the anesthetics might account for myotoxic effects, such as sustained contraction and eventual rigidity of both fast-twitch and masticatory muscles.


Correlates of psychological distress among adults with obesity during the COVID-19 pandemic.
The present study evaluated changes in stress and loneliness among participants with obesity engaged in weight loss self-management in the United States (US) during COVID-19, and identified factors that may increase risk or protect against psychosocial distress during this time. Participants who were enrolled in a weight self-management program prior to the COVID-19 pandemic (N = 55, 91% female, 36% Caucasian, mean age = 49.8 years) completed an online survey about social, economic and health behaviour changes during COVID-19 and their relationship to changes in perceived stress and loneliness. Perceived Stress (PSS-4), Loneliness (PROMIS loneliness and social isolation questionnaire). Compared to pre-COVID assessments, stress and loneliness increased 40% two months into the COVID-19 pandemic-related shutdown. Higher body mass index (BMI) and social distancing were associated with increases in both loneliness and stress. Alcohol intake was associated with increased stress, and working from home was associated with increased loneliness. Individuals with obesity endorsed increased stress and loneliness during COVID-19, which may be exacerbated among those with a higher BMI and greater adherence to social distancing guidelines. Ongoing attention to psychosocial well-being among individuals with obesity will remain imperative both during the ongoing pandemic and beyond.


[Anaplastic large-cell lymphoma CD30(+) ALK(+)].
We present a case of primary systemic anaplastic large-cell lymphoma, which manifested itself through skin involvement in a 32-year-old man. Only the third histological investigation with immunophenotyping resulted in the correct diagnosis of CD30(+) ALK(+) anaplastic large cell lymphoma. After combined chemotherapy and adjuvant radiotherapy, complete remission of the disease was achieved and one year after completion of therapy no relapse occurred. The diagnostic pitfalls and therapeutic options are discussed.


[Structural heterogeneity of chromatin preparations at the level of DNA topology].
The structural heterogeneity of calf thymus chromatin preparations was studied at the level of DNA topology by analysing the influence of ethidium bromide on the chromatin viscosity in deproteinizing medium. In 0.7 M NaCl the chromatin was separated into the fractions with linear DNA (3--36% in various preparations) and with supercoiled circular DNA (scc DNA), which differ from each other in their adhesive properties. Reduction of disulfide bonds in residual chromatin protein with 5% mercaptoethanol linearized scc DNA, present in chromatin preparations as nuclear matrix subunits containing some loops of scc DNA on the protein globule.


Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study.
To evaluate the associations of plasma bile acid metabolites, especially in early pregnancy, with gestational diabetes mellitus (GDM) risk among pregnant women. Plasma concentrations of 15 bile acid metabolites were measured in 645 women at early pregnancy from the Jiashan Birth Cohort using a liquid chromatography-tandem mass spectrometry metabolomics platform. Using logistic and cubic spline models, we examined associations between baseline plasma bile acid metabolites and GDM risk during mid-late pregnancy. A meta-analysis of prospective studies of bile acid and GDM risk was performed. The linear and nonlinear univariate models identified eight metabolites associated with GDM, including cholic acid, taurocholic acid (TCA), glycocholic acid, glycochenodeoxycholic acid, deoxycholic acid, lithocholic acid (LCA), ursodeoxycholic acid and taurolithocholic acid (all P <0.05). Multivariable analysis indicated that TCA and LCA levels were positively (odds ratio [OR] 2.07, 95% confidential interval [CI] 1.05, 3.96; P = 0.030) and negatively (OR 0.83, 95% CI 0.68, 1.01; P = 0.065) associated with GDM, respectively, after adjusting for confounders. The TCA-GDM association showed a positive linear shaped relationship (OR 2.07, 95% CI 1.05, 3.96; P = 0.030); while LCA was negatively related with GDM risk in linearity (OR 0.83, 95% CI 0.68, 1.01; P = 0.065). The meta-analysis of five studies showed a consistent bile acid and GDM association, with a risk ratio (RR) of 2.43 (1.95, 3.03). This study indicated that, the levels of circulating bile acids in early pregnancy were associated with risk of GDM, independent of GDM risk factors. Most GDM-associated bile acids were primary conjugated and secondary unconjugated bile acids.


Fibronectin signaling stimulates BNP gene transcription by inhibiting neuron-restrictive silencer element-dependent repression.
Brain natriuretic peptide (BNP) is a cardiac hormone mainly synthesized in ventricles and its expression is markedly increased in ventricular hypertrophy that involves the accumulation of extracellular matrix proteins, such as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP secretion accompanied by hypertrophic responses in vitro. To elucidate the regulatory mechanism for BNP gene transcription, we examined cis-acting elements downstream of Fn signaling in rat ventricular myocytes transfected with either the -1812 human BNP-luciferase reporter gene (-1812hBNP/Luc) or one of several truncated forms. A strong cis-repressor element was identified between -552 and -522 in myocytes plated on uncoated dishes. This region contains a neuron-restrictive silencer element (NRSE)-like element (NRSE(BNP)) that is 90% homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor (NRSF) is known to bind to NRSE and to silence transcription of genes containing NRSE. Deletion of NRSE(BNP) and dominant negative NRSF markedly increased the reporter activity in transfected cells, suggesting that the NRSE/NRSF system silences basal BNP gene transcription. When myocytes were cultured on Fn-coated dishes, the reporter activity of -1812hBNP/Luc was increased by approximately 600% compared with that on uncoated dishes. Interestingly, truncation from -552 to -522 reduced the Fn-inducible reporter activity. Moreover, deletion of NRSE(BNP) and dominant negative NRSF also inhibited the Fn-inducible reporter activity. Electrophoretic mobility shift assays showed that Fn signaling inhibited the binding activity of NRSF to NRSE(BNP). These results suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to inhibition of NRSE(BNP)-dependent repression of BNP gene transcription.


The motion of conventional and novel total ossicular replacement prostheses during changes in static pressure.
To investigate the motion of prostheses used to reconstruct ears with an absent stapes arch. We have studied the motion of conventional total ossicular replacement prostheses (TORPs) and a novel incus-stapes replica prosthesis (ISRP), which connects the malleus head to the footplate, during changes in middle ear pressure (+400 to -400 dPa) in fresh human temporal bones using digital video clips and photographs. The pressure in the (sealed) external auditory meatus was varied using a manual tympanometer. The displacements of the prostheses in the medial to lateral plane have been measured using the dimensioning tool of Corel Draw. During changes in static pressure, TORPs move more in the lateral to medial plane than ISRPs. The motion of ISRPs is similar to that of the intact ossicular chain. The ISRP design is less likely to damage the cochlea during changes in static pressure than a conventional TORP, but the maximum medial displacement of the TORPs studied was less than 0.1 mm.


The reaction of tris (hydroxymethyl) aminomethane with calf intestinal alkaline phosphatase.
The effect of tris (hydroxymethyl) aminomethane concentrations on the rate of calf intestinal alkaline phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate was studied, in the pH range 8-10, where no transphosphorylation reaction could be detected. Kinetic analysis of the results permitted description of the effect of Tris concentrations T on the rate of enzyme catalyzed hydrolysis (V) by the following equation: (see article). The rate-accelerating effect of Tris concentrations can be ascribed to two different mechanisms: At moderate Tris concentrations (0.01-0.20 M) the enzyme forms a reversible addition complex with a Tris molecule. This complex has an enhanced catalytic activity. We suggest that the binding of Tris to the enzyme could potentiate a second active site of the enzyme, due to its ionization effect upon an acidic group of the enzyme of pK = 8.9. The modest linear rate accelerating effect of Tris at high concentrations (0.20-0.60 M) could be ascribed to the change of the dielectric constant of the medium, the degree of solvation of the protein, or change in the tertiary structure of the enzyme.


Performance of bone-level implants with conical connections in the anterior maxilla: A 5-year prospective cohort study.
To assess clinical, radiographic and aesthetic outcomes, and satisfaction of patients treated with single implant restorations in the maxillary aesthetic region 5 years after final restoration. Sixty patients (29 male/31 female, mean age 37 years) with a missing anterior tooth in the maxilla (39 central incisors/10 lateral incisors/5 cuspids/6 first premolars) received a bone-level implant with conical connection. In 29 patients, a bone augmentation procedure was necessary before implant placement (autogenous bone grafts mixed with spongiosa granules). All implants (12 with 3.3 mm diameter/ 48 with 4.1 mm diameter) were loaded after 3 months of submerged healing. The restoration consisted of an individually designed full-zirconia abutment veneered with porcelain. Follow-up with clinical and radiographic assessment was conducted until 60 months after the final restoration. Aesthetic outcome of the restoration was determined with the Pink Esthetic Score-White Esthetic Score (PES-WES). Patient satisfaction was assessed with a VAS scale and satisfaction questionnaire. Fifty patients completed the 5-year follow-up. Implant survival was 100%, restoration survival 98%. Mean bone-level change was -0.13 ± 0.66 mm with a median (IQR) pocket probing depth of 2.75 [2.25; 3.25]. The mean PES and WES scores were 6.6 ± 1.7 and 7.8 ± 1.5, respectively. Patient satisfaction was high (92.1 ± 7.8 on 100 mm VAS scale). There were no differences between patients with or without a bone augmentation procedure. Bone-level implants with a conical connection are a reliable treatment option in single-tooth replacements in the maxillary aesthetic zone.


Diabetic gastroparesis-associated bezoar resolution via "cola-lysis".
Phytobezoars associated with diabetic gastroparesis are often sources of diminished quality of life for patients. Poor blood sugar control has been associated with increasing gastroparesis. For recipients of pancreas transplants to correct diabetes, phytobezoar treatment post-transplant can typically be limited to invasive procedures and prokinetic agents. We present the case of an alternative treatment to phytobezoar, cola libation, i.e., "cola-lysis."


In vitro cell culture models for ultrasound treatments using collagen-based scaffolds.
Applications involving ultrasound treatment as a therapeutic strategy have gained interest due to its enhanced tissue penetration, broad availability, and minimal invasiveness. Recently, ultrasound treatment has been utilized for applications such as controlled drug delivery, enhanced drug penetration, sonodynamic therapy for generating ROS species, and targeted tissue ablation. However, our ability to study and explore applications is limited by the lack of in vitro models that enable efficient and representative screening of ultrasound-based therapeutic strategies. There is a need for cell culture approaches that mimic the mechanical environment of native tissues, which can prevent uncontrolled cell lysis due to ultrasonic energy. We developed two-dimensional and three-dimensional collagen-based materials for culturing cells in vitro that withstand ultrasound treatment. We hypothesized that the collagen matrix mimics the extracellular matrix and absorb most of the energy from ultrasound treatment - similar to in vivo effects - thereby preventing uncontrolled cell lysis. In this study, we developed a strategy for fabricating both the 2D coatings and 3D hydrogels coatings and tested the viability of the cultured cells post different durations of ultrasound treatment.


PCR-based detection of resistance genes in anaerobic bacteria isolated from intra-abdominal infections.
Little information is available on the distribution of antimicrobial resistance genes in anaerobes in Japan. To understand the background of antimicrobial resistance in anaerobes involved in intra-abdominal infections, we investigated the distribution of eight antimicrobial resistance genes (cepA, cfiA, cfxA, ermF, ermB, mefA, tetQ, and nim) and a mutation in the gyrA gene in a total of 152 organisms (Bacteroides spp., Prevotella spp., Fusobacterium spp., Porphyromonas spp., Bilophila wadsworthia, Desulfovibrio desulfuricans, Veillonella spp., gram-positive cocci, and non-spore-forming gram-positive bacilli) isolated between 2003 and 2004 in Japan. The cepA gene was distributed primarily in Bacteroides fragilis. Gene cfxA was detected in about 9 % of the Bacteroides isolates and 75 % of the Prevotella spp. isolates and did not appear to contribute to cephamycin resistance. Two strains of B. fragilis contained the metallo-β-lactamase gene cfiA, but they did not produce the protein product. Gene tetQ was detected in about 81, 44, and 63 % of B. fragilis isolates, other Bacteroides spp., and Prevotella spp. isolates, respectively. The ermF gene was detected in 25, 13, 56, 64, and 16 % of Bacteroides spp., Prevotella spp., Fusobacterium spp., B. wadsworthia, and anaerobic cocci, respectively. Gene mefA was found in only 10 % of the B. fragilis strains and 3 % of the non-B. fragilis strains. Genes nim and ermB were not detected in any isolate. Substitution at position 82 (Ser to Phe) in gyrA was detected in B. fragilis isolates that were less susceptible or resistant to moxifloxacin. This study is the first report on the distribution of resistance genes in anaerobes isolated from intra-abdominal infections in Japan. We expect that the results might help in understanding the resistance mechanisms of specific anaerobes.


The "olfactostriatum" of snakes: a basal ganglia vomeronasal structure in tetrapods.
The olfactostriatum is a portion of the basal ganglia of snakes situated ventromedially to the nucleus accumbens proper. It receives a major vomeronasal input from the nucleus sphericus, the primary target of accessory olfactory bulb efferents. Recently, the ophidian olfactostriatum has been characterized on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and hodology (afferent and efferent connections). In contrast to the nucleus accumbens proper, the olfactostriatum is densely immunoreactive for serotonin and neuropeptide Y and sparsely immunoreactive for tyrosine hydroxylase. The nucleus accumbens proper and the olfactostriatum share most afferent connections except those originating in the nucleus sphericus, which are exclusively directed to the olfactostriatum. Similarly, the nucleus accumbens proper and the olfactostriatum show a similar pattern of efferent connections including those going to the ventral pallidum, although the olfactostriatum alone projects to the main and accessory olfactory bulbs as well as some amygdaloid nuclei. On the basis of its chemoarchitecture, the olfactostriatum resembles the mammalian ventral pallidum (but also the shell of the nucleus accumbens). Its connections, however, suggests that the olfactostriatum could be a specialized portion of the shell of nucleus accumbens extended more ventromedially than previously believed and devoted to processing vomeronasal information. Comparative data suggest that a similar structure is present in the basal ganglia of amphibians and mammals.


Evidence for oxygen-conserving diamond formation in redox-buffered subducted oceanic crust sampled as eclogite.
Cratonic eclogite is the product of oceanic crust subduction into the subcontinental lithospheric mantle, and it also is a fertile diamond source rock. In contrast to matrix minerals in magma-borne xenoliths, inclusions in diamond are shielded from external fluids, retaining more pristine information on the state of the eclogite source at the time of encapsulation. Vanadium is a multi-valent element and a widely used elemental redox proxy. Here, we show that that xenolithic garnet has lower average V abundances than garnet inclusions. This partly reflects crystal-chemical controls, whereby higher average temperatures recorded by inclusions, accompanied by enhanced Na2O and TiO2 partitioning into garnet, facilitate V incorporation at the expense of clinopyroxene. Unexpectedly, although diamond formation is strongly linked to metasomatism and xenoliths remained open systems, V concentrations are similar for bulk eclogites reconstructed from inclusions and from xenoliths. This suggests an oxygen-conserving mechanism for eclogitic diamond formation, and implies that eclogite is an efficient system to buffer fO2 over aeons of lithospheric mantle modification by subduction-derived and other fluids.


Optimisation of the use of sliding window deconvolution for comprehensive characterisation of trastuzumab and adalimumab charge variants by native high resolution mass spectrometry.
The biopharmaceutical industry continues to develop mAb-based biotherapeutics in increasing numbers. Due to their complexity, there are several critical quality attributes (CQAs) that need to be measured and controlled to guarantee product safety and efficacy. Charge variant analysis is a widely used method to monitor changes in product quality during the manufacturing process of monoclonal antibodies (mAbs) and, together with a bottom-up peptide centred approach, acts as a key analytical platform to fulfil regulatory requirements. Native MS measures biomolecules under conditions that preserve most aspects of protein tertiary and quaternary structure, enabling direct characterization of large intact proteins such as mAbs. The resulting native mass spectrum of a mAb is characterized by a narrower charge-state envelope that simplifies the spectra and also condenses the ion signals into fewer peaks, increasing the signal-to-noise ratio. Algorithmic spectral deconvolution is needed for routine accurate and rapid molecular weight determination, and consequently, multiple deconvolution algorithms have evolved over the past decade. Here, we demonstrate the utility of the sliding window algorithm as a robust and powerful deconvolution tool for comprehensive characterisation of charge variant analysis data for mAbs. Optimum performance is evaluated by studying the impact of critical software parameters on detection, identification and relative quantitation of protein isoforms. By combining molecular mass and retention time information, it was possible to identify multiple modifications on adalimumab and trastuzumab, both IgG1 mAbs, including lysine truncation, deamidation and succinimide formation, along with the N-glycan distribution of each of the identified charge variants. Sliding window deconvolution also provides a key benefit of low abundant variant detection in a single analysis and the ability to detect co-eluting components with different relative abundances. The studied mAbs demonstrate the algoritms applicability for efficient data processing of both simple and complex mAbs analysed using pH gradient cation exchange chromatography coupled to native mass spectrometry.


Antinflammatory and anticancer effects of terpenes from oily fractions of Teucruim alopecurus, blocker of IκBα kinase, through downregulation of NF-κB activation, potentiation of apoptosis and suppression of NF-κB-regulated gene expression.
Teucrium alopecurus is an endemic plant limited to southern Tunisia. In the present study, the chemical composition, anticancer and nuclear factor-κB (NF-κB) inhibitory effects of Teucrium alopecurus leaf essential oil was investigated. The analysis of Teucrium alopecurus (TA-1) with Gas Chromatography-Mass Spectrometry (GC/MS) showed that α-Bisabolol, (+)-epi-Bicyclosesquiphellandrene and α-Cadinol, were found in relatively high amounts (16.16%, 15.40% and 8.52%, respectively). Cell viability was determined by 3-(4-5-dimethylthiazol-2-yl) 2-5-diphenyl-tetrazolium (MTT) assay. Cell cycle and apoptosis assay were determined by flow cytometry. TA-1 functions as an anticancer agent by triggering apoptosis potentiated by chemotherapeutic agents and TNF in human myeloid leukemia cells (KBM5) through a mechanism involving poly(ADP-ribose) polymerase (PARP) cleavage and initiator and effector caspases activation. Moreover, electrophoretic mobility shift assay (EMSA) revealed that TA-1 downregulated nuclear localization of NF-κB and its phosphorylation induced by TNF-α and this, allows the suppression of the degradation and phosphorylation of IκB and the inhibition of the phosphorylation of p65 phosphorylation and the p50-p65 heterodimer nuclear translocation, causing attenuation of NF-κB-regulated antiapoptotic (Survivin, Bcl-2, c-IAP1/2, Bcl-xL, Mcl-1, and cFLIP), invasion (ICAM1), metasatsis (MMP-9), and angiogenesis (VEGF) gene expression in KBM5; and finally reporter gene expression. Furthermore, treatment with essential oil and TNF-α suppressed the NF-κB DNA binding activity. Finally, the activation of nuclear factor-κB induced by different plasmids (TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKβ) was inhibited following treatment with TA-1. Overall, TA-1 inhibits NF-κB activation and further growth and proliferation of cancer cells.


ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl.
A cDNA coding for ik3-2 (designated as ik3-2 from an interactor-2 with cdk3) was cloned by cross-hybridization with ik3-1 and RT-PCR. Analysis of amino acid sequence indicated that ik3-2 has the C-terminal cyclin-box-like region highly homologous to that of ik3-1 (identity in amino acids: 78%). On the other hand, the remainder of ik3-2 gene is not so similar to that of ik3-1. There are several regions other than the C-terminal cyclin-box-like region that are conserved between ik3-1 and ik3-2. In vivo binding assay indicated that like ik3-1, ik3-2 binds to cdk3, cdk5, and c-abl, although ik3-2 binds to cdk3 weakly as compared with ik3-1. The C-terminal cyclin-box-like region of ik3-2 (123 amino acids) is able to be associated with cdk5. Accordingly, ik3-2 is very similar to ik3-1 concerning its molecular interaction with other molecules, suggesting that ik3-2 function in the same biological field as ik3-1. Northern blot analysis indicated that ik3-2 is expressed ubiquitously all over tissues.


Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.
L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.


Change in perception of the quality of death in the intensive care unit by healthcare workers associated with the implementation of the "well-dying law".
The importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the "well-dying law" in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU. The Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed. After the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis. Our study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved.


Rapid annotation of interictal epileptiform discharges via template matching under Dynamic Time Warping.
EEG interpretation relies on experts who are in short supply. There is a great need for automated pattern recognition systems to assist with interpretation. However, attempts to develop such systems have been limited by insufficient expert-annotated data. To address these issues, we developed a system named NeuroBrowser for EEG review and rapid waveform annotation. At the core of NeuroBrowser lies on ultrafast template matching under Dynamic Time Warping, which substantially accelerates the task of annotation. Our results demonstrate that NeuroBrowser can reduce the time required for annotation of interictal epileptiform discharges by EEG experts by 20-90%, with an average of approximately 70%. In comparison with conventional manual EEG annotation, NeuroBrowser is able to save EEG experts approximately 70% on average of the time spent in annotating interictal epileptiform discharges. We have already extracted 19,000+ interictal epileptiform discharges from 100 patient EEG recordings. To our knowledge this represents the largest annotated database of interictal epileptiform discharges in existence. NeuroBrowser is an integrated system for rapid waveform annotation. While the algorithm is currently tailored to annotation of interictal epileptiform discharges in scalp EEG recordings, the concepts can be easily generalized to other waveforms and signal types.


Casein kinases: pleiotropic mediators of cellular regulation.
The present review on casein kinases focuses mainly on the possible metabolic role of CK-2, with special emphasis on its behavior in pathological tissues. From these data at least three ways to regulate CK-2 activity emerge: (i) CK-2 activity changes during embryogenesis, being high at certain stages of development and showing basal activity values at others; (ii) CK-2 activity can be enhanced in vitro by treatment of tissue culture cells with various growth factors and serum and (iii) CK-2 activity is constitutively enhanced in rapidly proliferating cells. The regulated CK-2 activity changes during embryogenesis cannot be explained as yet. In the case of the constitutive high expression of CK-2 in tumors, genetic changes may be responsible, e.g. through alterations of the regulatory genetic elements and/or regulation by specific transcription factors. In the case of serum induction, no genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2 subunits are highly conserved during evolution. The relationship between CK-2 alpha from humans and plants is still 73%. Similar relationships are reported for the beta-subunit. Chromosomal assignment of CK-2 alpha shows two gene loci, one of which is a pseudogene. They are located on different chromosomes. Expression of the CK-2 subunits in Escherichia coli and the Baculo expression system is shown. The recombinant subunits can self-assemble to a functional holoenzyme in vitro. Biochemical and biophysical analysis of the recombinant beta-subunit suggests it to be trifunctional in association with the alpha-subunit affecting: (i) stability, (ii) enzyme specificity and (iii) enzyme activity. The question where CK-2 and its subunits are located throughout the cell cycle has also been addressed, mainly because of the large discrepancies that still exist between results obtained by different investigators. Tissue-specific expression of CK-2 at the mRNA and at the protein level has also been given attention. The fact that the enzyme activity is surprisingly high in brain and low in heart and lung may be indicative of involvement of CK-2 in processes other than proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)


Monocyte to high-density lipoprotein ratio predict long-term clinical outcomes in patients with coronary heart disease: A meta-analysis of 9 studies.
A novel inflammation-related biomarker, the monocyte to high-density lipoprotein cholesterol ratio (MHR), had a great relation to the development and prognosis of coronary atherosclerotic heart disease. Current study was to investigate whether the MHR was a potential tool in predicting the mortality and major adverse cardiac events (MACEs) in patients suffering coronary heart disease (CHD) by meta-analysis. The Cochrane Library, PubMed, MEDLINE, Scopus, EMBASE, and Web of science were searched for relevant cohort studies published prior to February 10, 2022. The association between MHR and mortality/MACEs was analyzed in patients with CHD. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to estimate the strength of association. In the meta-analysis, a total of 9 studies of 11,345 patients with CHD were included. Compared with the low level of MHR group, the high MHR value was associated with higher long-term MACEs (HR = 1.72 95% CI 1.36-2.18, P < .001), long-term mortality (HR = 1.71, 95% CI 1.10-2.66, P = .017), and in-hospital mortality/MACEs (HR = 2.82, 95% CI = 1.07-7.41, P = .036). This study suggested that increased MHR value might be associated with higher long-term mortality and long-term MACEs in CHD patients. MHR might serve as a potential prognostic indicator for risk stratification in patients with CHD.


Induced hypothermia as a new approach to lung rest for the acutely injured lung.
To investigate whether low-frequency ventilation during hypothermia could attenuate lung injury associated with endotoxin and mechanical ventilation. : Experimental animal study. University-affiliated animal laboratory. Forty-eight Sprague-Dawley rats. : Lipopolysaccharide was administered to rats intratracheally to induce acute lung injury. After 1 hr of this treatment, animals were assigned to normothermia-only (NO, rectal temperature 37 degrees C, ventilatory frequency 90/min), normothermia-lung rest (NR, 37 degrees C, 45/min), hypothermia-only (HO, 27 degrees C, 90/min), or hypothermia-lung rest (HR, 27 degrees C, 45/min). After 1 hr of injurious ventilation, the lungs of the rats were removed for bronchoalveolar lavage and histologic examination. Compared with the normothermia groups (NO, NR), the neutrophil counts (per milliliter) (NO, 7708 +/- 5704; NR, 10,479 +/- 11,152; HO, 1638 +/- 955; HR, 805 +/- 591) and interleukin-1beta levels (pg/mL) (1180 +/- 439, 1081 +/- 652, 620 +/- 426, 420 +/- 182, respectively) in the bronchoalveolar lavage fluid, the wet-to-dry lung weight ratios (6.0 +/- 0.4, 5.7 +/- 0.4, 5.6 +/- 0.2, 5.2 +/- 0.2, respectively), and histologic acute lung injury scores (8.3 +/- 2.7, 10.4 +/- 3.1, 3.5 +/- 2.1, 3.1 +/- 2.2, respectively) of the hypothermia groups (HO, HR) were lower (all p < .001). Compared with the HO group, the neutrophil counts and protein content (HO, 1367 +/- 490 mug/mL vs. HR, 831 +/- 369 mug/mL) in the bronchoalveolar lavage fluid, the serum lactate dehydrogenase levels (units/mL) (9.1 +/- 3.6 vs. 5.3 +/- 1.5), and the wet-to-dry lung weight ratios of the HR group were lower (all p < .05). Reduction of ventilatory frequency in conjunction with hypothermia attenuated many variables of acute lung injury in rats. Use of hypothermia could be exploited as a new approach to lung rest for the ventilatory management of the acutely injured lung.


Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer.
The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.


3-[(4-Phenyl-piperazin-1-yl)meth-yl]-5-(thio-phen-2-yl)-2,3-di-hydro-1,3,4-oxa-diazole-2-thione.
In the title compound, C17H18N4OS2, the 2-thienyl ring is disordered over two co-planar, opposite orientations in a 0.684 (2): 0.316 ratio. The 1,3,4-oxa-diazole ring is almost co-planar with the attached 2-thienyl ring [dihedral angles of 5.34 (19) and 4.8 (5)° for the major and minor components, respectively]. The relative disposition of the thione- and ring-S atoms is anti for the major orientation of the 2-thienyl residue. Overall, the shape of the mol-ecule approximates the letter V. In the crystal, a three-dimensional architecture is consolidated by a combination of weak C-H⋯S and C-H⋯π contacts.


TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL.
Early diagnosis of cutaneous T cell lymphoma (CTCL) is difficult and takes on average 6 years after presentation, in part because the clinical appearance and histopathology of CTCL can resemble that of benign inflammatory skin diseases. Detection of a malignant T cell clone is critical in making the diagnosis of CTCL, but the T cell receptor γ (TCRγ) polymerase chain reaction (PCR) analysis in current clinical use detects clones in only a subset of patients. High-throughput TCR sequencing (HTS) detected T cell clones in 46 of 46 CTCL patients, was more sensitive and specific than TCRγ PCR, and successfully discriminated CTCL from benign inflammatory diseases. HTS also accurately assessed responses to therapy and facilitated diagnosis of disease recurrence. In patients with new skin lesions and no involvement of blood by flow cytometry, HTS demonstrated hematogenous spread of small numbers of malignant T cells. Analysis of CTCL TCRγ genes demonstrated that CTCL is a malignancy derived from mature T cells. There was a maximal T cell density in skin in benign inflammatory diseases that was exceeded in CTCL, suggesting that a niche of finite size may exist for benign T cells in skin. Last, immunostaining demonstrated that the malignant T cell clones in mycosis fungoides and leukemic CTCL localized to different anatomic compartments in the skin. In summary, HTS accurately diagnosed CTCL in all stages, discriminated CTCL from benign inflammatory skin diseases, and provided insights into the cell of origin and location of malignant CTCL cells in skin.


Automatic digital contrast enhancement of radiotherapy films.
The practice of radiotherapy involves the precise geometric localization of both anatomic and non-anatomic structures using radiographs which are typically of very low contrast. Portal and verification films suffer from poor contrast as a result of the dominance of Compton interactions at therapeutic energies, and implant localization films often are degraded by extreme patient thickness (lateral pelvis) or projection of bony structures (head and neck). Automatic contrast enhancement techniques developed and proven for optimization of the display of digitally produced images such as CT have been applied to radiotherapy films to improve contrast and augment readability. This approach has become viable only recently with the advent of high speed, high resolution film digitizers and laser cameras and the evolution of sufficiently powerful computer hardware.


Correction: Garcia-Gonzalez, D.; Rivero, D.; Fernandez-Blanco, E.; Luaces, M.R. A Public Domain Dataset for Real-Life Human Activity Recognition Using Smartphone Sensors. Sensors 2020, 20, 2200.
The authors wish to make the following corrections to this paper [...].


DNA sequence based typing of swine leukocyte antigens in Yucatan miniature pigs.
We have established a breeding program to develop additional lines of swine leukocyte antigens (SLA) homozygous miniature pigs derived from the Yucatan Miniature Pig. Yucatan pigs have been used extensively in biomedical research since the 1970s and are known for their docile nature and small size. The breed has no consanguinity with the Hormel or Pittman-Moore breeds used to produce the NIH Miniature Pigs, the only other SLA homozygous miniature pigs in the USA. SLA typing was initially done by restriction fragment length polymorphism. Then a cDNA library was constructed using spleen cells from these pigs, from which we cloned and sequenced nearly all alleles for the SLA-1, 3, 2, 6, DRB1, DQA and DQB1 loci. Four SLA homozygous lines were established with haplotypes that we have designated 'w, x, y and z'. An SLA class I/II crossover haplotype, designated 'q', with the SLA class I alleles of 'w' and the SLA class II alleles of 'z' was discovered and used to establish a fifth line. The cDNA sequences were used to develop locus specific primers for each locus and an reverse transcription-polymerase chain reaction sequence based typing (SBT) method. We have used this method to perform SBT on SLA homozygous Yucatan pigs with these haplotypes and on the NIH pig 'a, c and d' haplotypes. These pig lines represent a new resource for transplantation research and the methods we describe can be used to SLA type any herd of pigs.


Presence of Ras guanyl nucleotide-releasing protein in striosomes of the mature and developing rat.
Ras signal transduction pathways have been implicated as key regulators in neuroplasticity and synaptic transmission in the brain. These pathways can be modulated by Ras guanyl nucleotide exchange factors, (GEF) which activate Ras proteins by catalysing the exchange of GDP for GTP. Ras guanyl nucleotide-releasing protein (RasGRP), a recently discovered Ras GEF, that links diacylglycerol and probably calcium to Ras signaling pathways, is expressed in brain as well as in T-cells. Here, we have used a highly selective monoclonal antibody against RasGRP to localize this protein within the striatum and related forebrain structures of developing and adult rats. RasGRP immunolabeling was found to be widespread in the mature and developing rat forebrain. Most notably, it presented a prominent patchy distribution throughout the striatum at birth and at all postnatal ages examined. These patches were found to correspond with the striosomal compartment of the striatum, as identified by micro-opioid receptor labeling in the adult. RasGRP-immunoreactivity was also observed in the matrix-like compartment surrounding these patches/striosomes but appeared later in development and was always weaker than in the patches. In both striatal compartments, RasGRP was exclusively expressed by medium-sized spiny neurons and showed no preference for neurons that project either directly or indirectly to the substantia nigra. At the ultrastructural level, immunogold labeling of RasGRP was confined to the cell bodies and dendritic shafts of these output neurons. We conclude that the prominent expression of RasGRP in striosomes may be of significance for diacylglycerol signaling in the striatum, and could be of importance for the processing of limbic-related activity within the basal ganglia.


First report of Salmonella enterica serotype panama meningitis associated with consumption of contaminated breast milk by a neonate.
Salmonella enterica serotype Panama is capable of causing severe infection in children and is often transmitted via contaminated food. Here, we present the first documented case of serotype Panama infection that was acquired through the consumption of contaminated breast milk. The mother excreted the organism asymptomatically for at least 2 weeks.


A watershed water quality prediction model based on attention mechanism and Bi-LSTM.
Accurate prediction of water quality contributes to the intelligent management and control of watershed ecology. Water Quality data has time series characteristics, but the existing models only focus on the forward time series when LSTM is introduced and do not consider the effect of the reverse time series on the model. Also did not take into account the different contributions of water quality sequences to the model at different moments. In order to solve this problem, this paper proposes a watershed water quality prediction model called AT-BILSTM. The model mainly contains a Bi-LSTM layer and a temporal attention layer and introduces an attention mechanism after bidirectional feature extraction of water quality time series data to highlight the data series that have a critical impact on the prediction results. The effectiveness of the method was verified with actual datasets from four monitoring stations in Lanzhou section of the Yellow River basin in China. After comparing with the reference model, the results show that the proposed model combines the bidirectional nonlinear mapping capability of Bi-LSTM and the feature weighting feature of the attention mechanism. Taking Fuhe Bridge as an example, compared with the original LSTM model, the RMSE and MAE of the model are reduced to 0.101 and 0.059, respectively, and the R2 is improved to 0.970, which has the best prediction performance among the four cross-sections and can provide a decision basis for the comprehensive water quality management and pollutant control in the basin.


Bacterial Inhibition Mechanism of Rhamnolipid-Modified β-Carotene/Rutinoside Complex Liposomes.
In this study, a new cholesterol-free delivery system named RL-βC-Rts was developed using rhamnolipid (RL) as the surfactant and encapsulating both β-carotene (βC) and rutinoside (Rts). The purpose was to examine its antibacterial properties against four food-borne pathogenic microorganisms including Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. m), and Salmonella typhimurium (S. typhimurium) and to investigate the mechanism behind the inhibition. Results from bacterial viability tests and minimum inhibitory concentration (MIC) showed RL-βC-Rts possessed antibacterial activity. Upon further examination of the cell membrane potential, it was observed that E. coli, S. aureus, L. m, and S. typhimurium exhibited a reduction in mean fluorescence intensity by 50.17%, 34.07%, 34.12%, and 47.05%, respectively. These decreases suggested damage to the structure of the cell membrane, which subsequently resulted in the discharge of proteins from the bacteria and the consequential impairment of crucial functions. This was supported by alterations in protein concentration. The results of the RT-qPCR showcased that the expression of genes associated with energy metabolism, tricarboxylic acid cycle, DNA metabolism, virulence factor formation and cell membrane formation could be suppressed by RL-βC-Rts. The online version contains supplementary material available at 10.1007/s12088-023-01077-6.


Trial insertion procedure for milled lithium disilicate restorations in the precrystallized state.
A treatment protocol with lithium disilicate restorations and a computer-aided design and computer-aided manufacturing (CAD/CAM) fabrication process is proposed for the restoration of teeth in the esthetic zone. The technique involves trial insertion of restorations at the precrystallized stage, allowing verification of the marginal fit and evaluation of the internal adaptation and overall esthetic plan to ensure an optimal clinical result for the definitive restorations. Furthermore, this procedure allows most adjustments to the lithium disilicate ceramic to be made before crystallization and minimizes potential surface and subsurface damage to the definitive restorations.


A congener-specific modelling approach for the transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls from feed to eggs of laying hens.
Calibration of a kinetic model for the transfer of PCDD/Fs and dl-PCBs from feed to the hen's body and eggs was thus far restricted to the total TEQ concentration, i.e. the summed concentrations of PCDD/Fs and dl-PCBs expressed in terms of equivalents of 2,3,7,8-TCDD. However, this approach may lead to over- or underestimation of the transfer if the mixture contains congeners with kinetic characteristics which differ considerably from those used in such a model. This paper extends a previous transfer model of PCDD/Fs and dl-PCBs from feed to egg yolk fat and abdominal fat of high production laying hens, based on the total TEQ approach, to the level of individual congeners. Both modelling approaches are compared and the new approach is presented as a webtool application. This congener-specific approach enabled the calibration of 25 of the 29 relevant PCDD/F and dl-PCB congeners with respect to their individual transfer characteristics to body fat and egg yolk fat and their clearance from the body. Limitations of the available experimental data prevented the calibration of 1,2,3,4,6,7,8-HpCDD, OCDD, OCDF and PCB 123. The fraction transferred to egg yolk fat after long-term daily intake of contaminated feed was found to be at least 0.78 for 2,3,7,8-TCDD, 0.75 for PeCDD, 0.42-0.61 for HxCDDs, 0.70 for 2,3,7,8-TCDF, 0.71 for PeCDF, 0.54-0.60 for HxCDFs, 0.18-0.24 for HpCDFs and 0.89-1.00 for dl-PCBs. Various experimental and feed incident mixtures were used to compare the total TEQ- model with the congener-specific approach. An overestimation of the transfer by the total TEQ method was shown in particular for mixtures with a substantial contribution of hexa-, hepta- and octa-PCDD/Fs to the total TEQ level.


Urinary retention in a general rehabilitation unit: prevalence, clinical outcome, and the role of screening.
To document the prevalence of, risk factors for, and outcomes of, urinary retention (UR). Prospective observational study. A subacute general (predominantly geriatric) rehabilitation unit. Three hundred nineteen consecutive patients (196 women, 123 men). Twenty-two patients were catheterized for acute UR in the acute facility prior to transfer to rehabilitation. Patients admitted without catheters (n=297) had their postvoid residual (PVR) volumes assessed via a bladder scanner within 72 hours of admission. PVR volumes of 150 mL or more were considered abnormal. PVR volumes in the 297 "asymptomatic" patients were 150 mL or more in 64 (21.5%) patients. The risk of UR was greatest among male patients who had lower admission FIM instrument scores, neurologic disorders (eg, stroke or multiple sclerosis), cognitive impairment, urinary incontinence, a history of previous prostate, bladder, or voiding problems, were taking anticholinergic medications, or were immobile. Patients with UR were significantly more likely to have a urinary tract infection at admission, have urinary incontinence on discharge, and to be discharged with referrals for community services for personal care or to residential care. Although patients with UR on admission had a lower discharge FIM score, they generally showed a greater degree of improvement in their FIM scores during their stay. Clinically unsuspected UR is common in patients admitted to a general rehabilitation unit. We recommend that all patients be screened for PVR on admission as an aid in bladder management.


Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression.
Acute lung injury (ALI) together with acute respiratory distress syndrome (ARDS) are associated with high rate of mortality and morbidity in patients. In the current study, the anti-inflammatory effects of continentalic acid (CNT) in LPS-induced acute lung injury model was explored. The acute lung injury model was established by administering LPS (5 mg/kg) intraperitonealy. Following LPS administration, the survival rate, temperature changes and lung Wet/Dry ratio were assessed. The antioxidants (GSH, GST, Catalase and SOD) and oxidative stress markers (MDA, NO, MPO) were evaluated in all the treated groups. Similarly, the cytokines such as IL-1β, IL-6 and TNF-α were analyzed using ELISA assay. The histological changes were determined using H and E staining, while Nrf2 and iNOS level were determined using immunohistochemistry analysis. The molecular docking analysis was performed to assess the pharmacokinetics parameters and interaction of the CNT with various protein targets. The results showed that CNT dose dependently (10, 50 and 100 mg/kg) reduced mortality rate, body temperature and lungs Wet/Dry ratio. CNT post-treatment significantly inhibited LPS-induced production of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. The CNT post-treatment markedly improved the hematological parameters, while significantly reduced the MPO (indicator of the neutrophilic infiltration) activity compared to the LPS treated group. Furthermore, the CNT (100 mg/kg) post-administration remarkably inhibited the lung Wet/Dry ratio. The CNT (100 mg/kg) treated group showed marked reduction in the oxidative stress markers such as malonaldehyde (MDA) and Nitric oxide (NO) concentration, while induced the level of the anti-oxidant enzymes such as GST, GSH, Catalase and SOD. Similarly, the CNT markedly reduced the iNOS expression level, while induced the Nrf2 protein expression. Additionally, the molecular docking study showed significant binding interaction with the Nrf2, p65, Keap1, HO-1, IL-1β, IL-6, TNF-α and COX-2, while exhibited excellent physicochemical properties. The CNT showed marked protection against the LPS-induced lung injury and improved the behavioral, biochemical and histological parameters. Furthermore, the CNT showed significant interaction with several protein targets and exhibited better physicochemical properties.


Therapeutic options for biliary tract disease in advanced cirrhosis.
Between 1979 and 1984, 21 male cirrhotic patients with advanced liver disease, cholecystitis, and jaundice were seen. Eight patients had persistent symptoms of acute cholecystitis despite intense symptoms of acute cholecystitis despite intense medical management. Of these patients, five underwent cholecystostomy and survived. The other three patients had cholecystectomy and one died. Thirteen patients presented with jaundice. Twelve patients underwent endoscopic retrograde cholangiography which revealed gallbladder stones in four but no stones in the common bile duct. They did not undergo further surgical procedures. One patient presented with jaundice, cholangitis, and pancreatitis was found to have stones in the common bile duct and underwent endoscopic sphincterotomy with removal of multiple small, pigmented stones. This patient died from sepsis and renal failure 37 days after sphincterotomy. Endoscopic retrograde cholangiography was unsuccessful in four patients who later underwent percutaneous transhepatic cholangiography which revealed stones in one and cirrhotic ductal changes in three. The remaining jaundiced patient underwent cholecystectomy and common bile duct exploration which revealed no ductal stones. This patient died 21 days after operation from sepsis and multiple organ system failure. Three of five patients with gallstones on endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography died, but none of the deaths were due to biliary tract disease. At last follow-up the two surviving patients were asymptomatic. The overall mortality rate was 14 percent (3 of 21 patients). Cholecystostomy in cirrhotic patients with advanced liver disease and acute cholecystitis is associated with minimal mortality and morbidity. Cirrhotic patients with jaundice are probably best evaluated initially by endoscopic retrograde cholangiopancreatography which is safe, diagnostic, and sometimes therapeutic.


Effects of anaerobic incubation on the desorption of polycyclic aromatic hydrocarbons from contaminated soils.
Incubation of field-contaminated soil under anaerobic conditions can lead to increased mobilization of polycyclic aromatic hydrocarbons (PAHs) into water. In the present study, we evaluated the effects of anaerobic incubation on the rate and extent of desorption of PAH from two field-contaminated soil samples. One was a highly contaminated soil from a former wood-preserving site that had not been subject to previous treatment; the other was a soil from a former manufactured-gas plant site that had been treated in an aerobic bioreactor. A two-site desorption model was applied to quantify the fast and slowly desorbing fractions of each PAH and the corresponding first-order rate constants for each fraction. For most of the PAHs, the total amount desorbed after 18 d from anaerobically incubated samples was significantly greater than that from their counterparts not subjected to anaerobic incubation, but the overall effect was modest. The rate constant corresponding to the slowly desorbing fraction (k(2)) was much higher for the samples incubated under active anaerobic conditions than that for the controls, implying anaerobic incubation had the greatest influence on the soil compartments controlling the slow release of PAHs. Anaerobic incubation had little to no effect on the rapidly desorbing fraction.


[The role of epidemiologic research of the natural history of cancer for evaluating cancer screening programs--a prospective study of colorectal polyps on the occurrence of colorectal cancer].
In order to elucidate the natural history of colorectal polyps and to examine the effectiveness of endoscopic polypectomy in reducing the incidence of colorectal cancer, we conducted a retrospective cohort study of all patients who had undergone endoscopic examination at the Center for Adult Diseases, Osaka in 1970-82. The study subjects consist of 653 non-polyp cases and 431 colorectal polyp cases including 222 cases treated by endoscopic polypectomy. These were followed up until the end of 1985 by the method of a record linkage with the Osaka Cancer Registry's file. The colorectal polyp group and the endoscopic polypectomy group experienced 4.4 and 2.9 times, respectively, as much incidence of colorectal cancer as the non-polyp group. The magnitude of the prevented fraction by the use of endoscopic polypectomy was estimated at 31.3%. A large-scale and long-term study is necessary to elucidate the original study purpose.


[Controlled obturator nerve block using electrostimulation: prevention of the stimulation of the obturator nerve during resection of the lateral walls of the bladder].
An adductor contraction secondary to obturator nerve stimulation can occur during transurethral resection of a lateral bladder lesion and then can induce bladder perforation or hamper complete resection. Many technique have been advocated but they are ineffective or unreliable. Obturator nerve blockade in the obturator canal by local anesthesia with control by nerve stimulator can prevent these complications. The technique described, has been used in 12 patients it is reliable, fast and easy to perform.


K cell activity of normal and chronic lymphocytic leukaemia lymphocytes: association with lymphocytes bearing receptors for human C3b.
Blood lymphocytes of patients with chronic lymphocytic leukaemia (CLL) and of normal individuals were depleted of EAC3b- or EAC3d-rosette-forming cells (RFC), respectively and assayed for K-cell activity in a system measuring antibody-dependent-cell-mediated cytotoxicity (ADCC). K-cell activity was found to be associated with a cell population bearing receptors for C3b.


Infertility treatment. An approach for the general practitioner.
An approach to the management of the infertile couple in general practice is presented. Attention is paid particularly to those aspects of treatment which the interested practitioner may provide himself and the stage at which referral should be sought; insight is also given into some of the 'specialist aspects' of infertility.


Decreased platelet imipramine binding in Tourette syndrome children with obsessive-compulsive disorder.
[3H]Imipramine binding to blood platelets was assessed in eight untreated Tourette syndrome (TS) children, nine drug-free TS children with obsessive-compulsive disorder (OCD), and nine age-matched and gender-matched control subjects. The density of [3H]imipramine binding sites in TS + OCD patients was significantly lower compared with TS-OCD patients (28%) as well as when compared with controls (31%). This alteration was not accompanied by differences in the affinity of the binding site to the ligand. The decreased density of the platelet serotonin "transporter" might implicate the involvement of the serotonergic system in the pathophysiology of OCD in TS patients, but not in TS per se.


Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment.
Time-lapse microscopy, retrospective immunohistochemistry, and cultured hippocampal neurons were used to determine the time frame of individual glutamatergic synapse assembly and the temporal order in which specific molecules accumulate at new synaptic junctions. New presynaptic boutons capable of activity-evoked vesicle recycling were observed to form within 30 min of initial axodendritic contact. Clusters of the presynaptic active zone protein Bassoon were present in all new boutons. Conversely, clusters of the postsynaptic molecule SAP90/PSD-95 and glutamate receptors were found on average only approximately 45 min after such boutons were first detected. AMPA- and NMDA-type glutamate receptors displayed similar clustering kinetics. These findings suggest that glutamatergic synapse assembly can occur within 1-2 hr after initial contact and that presynaptic differentiation may precede postsynaptic differentiation.


The pituitary gland: embryology, physiology, and pathophysiology.
The pituitary gland, the "master gland" of the body, is composed of endocrine cells, which secrete hormones essential for homeostasis. The gland consists of the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary), two unique structures that differ anatomically and functionally. The neurohypophysis is innervated by nerve cells in the hypothalamus and forms the connection between it and the pituitary gland. The hypothalamus stimulates release and inhibition of pituitary hormones. The neurohypophysis secretes oxytocin and antidiuretic hormone. The adenohypophysis is composed of three structures: the pars distalis, the pars intermedia, and the pars tuberalis. The anterior pituitary (pars distalis) is responsible for the release of hormones that include growth hormone, prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and melanocyte-stimulating hormone. Disorders of the pituitary are predominately those of insufficient hormone release and may have profound effects on the neonate. The potential causes of and clinical symptomatology that may accompany pituitary hormone insufficiency in the neonatal period are explored.


Molecular Fingerprint and Dominant Environmental Factors of Nitrite-Dependent Anaerobic Methane-Oxidizing Bacteria in Sediments from the Yellow River Estuary, China.
Nitrite-dependent anaerobic methane oxidation (n-damo) is performed by "Candidatus Methylomirabilis oxyfera" (M. oxyfera), which connects the carbon and nitrogen global nutrient cycles. In the present study, M. oxyfera-like bacteria sequences were successfully recovered from Yellow River Estuary sediments using specific primers for 16S rRNA and pmoA genes. A M. oxyfera-like sequences analysis based on the 16S rRNA gene revealed greater diversity compared with the pmoA gene; the 16S rRNA gene sequences retrieved from the Yellow River Estuary sediments belong to groups A as well as B and were mainly found in freshwater habitats. Quantitative PCR showed that 16S rRNA gene abundance varied from 9.28±0.11×10(3) to 2.10±0.13×10(5) copies g(-1) (dry weight), and the pmoA gene abundance ranged from 8.63±0.50×10(3) to 1.83±0.18×10(5) copies g(-1) (dry weight). A correlation analysis showed that the total organic carbon (TOC) and ammonium (NH4(+)) as well as the ratio of total phosphorus to total nitrogen (TP/TN) influenced the M. oxyfera-like bacteria distribution in the Yellow River Estuary sediments. These findings will aid in understanding the n-damo bacterial distribution pattern as well as their correlation with surrounding environmental factors in temperate estuarine ecosystems.


[Effect of tageflar, a synthetic analog of L-enkephalin, on the morphogenesis of experimental pancreatitis].
It has been substantiated that the use of a new synthetic drug tageflar analogous to L-enkephalin was accompanied by the depression in pancreatic enzyme activity in the blood of rats, acceleration of necrotic and lytic processes in irreversibly damaged exocrine pancreocytes in the course of experimental pancreatitis. The drug promoted microcirculation retention in the injury zone and acceleration of the arrangement and elimination of necrotic glandular tissue. The influence of tagaflar diminished the extent of perifocal necrobiotic zone and suppressed sclerotic processes and pancreatic lipomatosis.


W-boson production in TMD factorization.
At hadron colliders, the differential cross section for W production can be factorized and it is sensitive transverse momentum dependent distributions (TMD) for low boson transverse momentum. While, often, the corresponding non-perturbative QCD contributions are extrapolated from Z boson production, here we use an existing extraction (based on the code Artemide) of TMD which includes data coming from Drell-Yan and semi-inclusive deep inelastic scattering, to provide checks and predictions for the W case. Including fiducial cuts with different configurations and kinematical power corrections, we consider transverse momentum dependent cross sections within several intervals of the vector boson transverse mass. We perform the same study for the p T W - / p T W + and p T Z / p T W distributions. We compare our predictions with recent extractions of these quantities at ATLAS and CMS and results from TeVatron. The results encourage a broader experimental and phenomenological work, and a deeper study of TMD for the W case.


A central mechanism of action for taurine: osmoregulation, bivalent cations, and excitation threshold.
A postulated zinc-taurine complex, with a zinc affinity intermediate between that for glutamic acid dehydrogenase and the calcium binding protein(s), provides an explanation for a series of seemingly unrelated biochemical and physiological effects of taurine. The proposed complex suggests a central mechanism for the action of taurine, such as a bicarbonate and pH dependent influence on calcium and zinc movements (and vice versa), the osmoregulatory role of taurine, and its effect on the excitation threshold.


Small object intelligent detection method based on adaptive recursive feature pyramid.
As we all know, YOLOv4 can achieve excellent detection performance in object detection and has been effectively applied in many fields. However, the inconsistency of scale features affects the prediction accuracy of the path aggregation network (PANet) in YOLOv4 for small objects, resulting in low detection accuracy. This paper presents YOLOv4, which uses an adaptive recursive path aggregation network (AR-PANet) to improve the detection accuracy of small objects. First, the output characteristics of the PANet are fed back into the backbone network by using a recursive structure to enrich the characteristic information of the object. Second, an adaptive approach is developed to eliminate conflicting information in multi-scale feature space, thereby enhancing scale invariance and promoting feature extraction accuracy for small objects. Finally, the CBAM is used to map the multi-scale features obtained from the AR-PANet to independent channels and spatial dimensions to achieve feature refinement, thus improving the detection accuracy of small objects. Experimental results show that our proposed method can effectively improve the accuracy of small object detection in multiple datasets, addressing this challenging problem with impressive results. Thus, our proposed approach has great potential and valuable applications in the fields of remote sensing and intelligent transportation.