Long-term effects of vaginal dissection on the innervation of the striated urethral sphincter.
To study the long-term effects of vaginal dissection on the innervation of the striated urethral sphincter. Perineal nerve terminal motor latency was measured before and 8 weeks and 1 year after anterior colporrhaphy, colpoperineoplasty, and vaginal hysterectomy in 33 women, 19 of whom also underwent endoscopic suspension of the bladder neck. In the entire series, the mean perineal nerve terminal motor latency was prolonged before surgery over that in normal continent women and further prolonged 8 weeks and 1 year postoperatively. In the subjects who underwent vaginal hysterectomy and anterior colporrhaphy, perineal motor latencies were not significantly prolonged at the 8-week postoperative follow-up and had almost returned to preoperative values 1 year later. However, in those who underwent additional endoscopic bladder neck suspension, perineal motor latencies were prolonged at both postoperative follow-up examinations. Perineal motor latencies were unchanged 1 year postoperatively in continent patients (N = 19) but were prolonged in incontinent patients (N = 14). Vaginal dissection, especially during endoscopic bladder neck suspension, can worsen preexisting perineal neuropathy in patients with pelvic relaxation and stress incontinence.


[Methotrexate-induced changes in the concentration of antibodies to mutaded citrullinated vimentin in blood serum of patients with rheumatoid arthritis].
To study effects of methotrexate on the titer of antibodies to mutated citrullinated vimentin (anti-MCV) and ascertain possibility of using this marker for control of treatment results and choice of individual effective dose of the drug. A 12-month trial included 76 patients with verified rheumatoid arthritis (RA). Methotrexate per os was given in a dose 7.5-10 mg/week to 44 (57.9%) patients, 25 patients received no basic therapy. Anti-MCV (IU/ml) were detected with commercial chemicals made in Germany (ORGENTEC). RA patients given methotrexate doses 7.5 and 10 mg/week and untreated with basic anti-inflammatory drugs showed no significant differences by basic clinical and device parameters, level of anti-MCV at primary examination and 12 months later. Anti-MCV titer cannot be used for control of efficacy of methotrexate treatment in doses 75 and 10 mg/week, choice of individual effective doses.


Evidence of rhythmic inhibitory synaptic influences in hindlimb motoneurons during fictive locomotion in the thalamic cat.
Intracellular recordings of various motoneurons of proximal hindlimb muscles were performed on thalamic paralyzed cats, during fictive locomotion that was either spontaneous or evoked by stimulation of the subthalamic region. In motoneurons innervating sartorius (medialis and lateralis), vasti (intermedius, medialis and lateralis) and anterior biceps-semimembranous, one depolarization occurred in each locomotor cycle, alternating with a phase of repolarization that was synchronous with the activation of the antagonistic muscle nerve. This latter phase could be decreased or reversed by intracellular injection of chloride ions or current, revealing the presence of inhibitory inputs onto motoneurons. The pattern of membrane potential variations was more complex in motoneurons of rectus femoris and posterior biceps-semitendinosus muscles, but phases of chloride dependent inhibition were nevertheless identified, mainly during the sartorius nerve activation in the case of rectus femoris, and during the vasti and anterior biceps-semimembranosus nerve activations in the case of posterior biceps-semitendinosus. These inhibitory influences were shown to be controlled by the level of activity in exteroceptive afferents. The characteristics of the excitatory and inhibitory inputs to the hindlimb motoneurons identified here are discussed in relation with the organization of the central pattern generator for locomotion.


Toxoplasmic meningoencephalitis in an immunocompetent host.
Central nervous system involvement due to toxoplasmosis in an immunocompetent host is very rare. We report a case of an immunocompetent patient who presented with suspected tuberculous meningoencephalitis but showed no clinical response to antitubercular therapy. Later, toxoplasmic meningoencephalitis was proved by positive serological testing for toxoplasmosis, supportive magnetic resonance imaging findings of the brain and a therapeutic response to co-trimoxazole and prednisolone. Therefore, toxoplasmosis should be considered in cases of suspected tuberculous meningoencephalitis that fail to respond to specific therapy.


Ocular toxicity of intravitreous transforming growth factor-beta 1.
To evaluate the ocular toxicity of intravitreous transforming growth factor-beta 1 (TGF-beta(1)). Eyes of New Zealand white rabbits were injected intravitreally with TGF-beta(1) in doses of 20, 10, 5, 1 or 0.5 micrograms. Electroretinography and clinical examination were performed before and after the injection. At either 10 or 30 days after injection, the eyes were enucleated and examined histologically. The endothelium of fresh corneas, which had received 20 micrograms TGF-beta(1) or nothing, were checked 5 days after injection. Corneal opacity was caused by doses > or = 10 micrograms in 7 of 7 eyes; by doses of 5 micrograms in 3 of 4 eyes; and by doses of 1 microgram in 1 of 4 eyes. Doses > or = 5 micrograms also caused pannus formation in 15 of 16 eyes. Ten days after injection there was some decrease in B-wave amplitude on electroretinography. Thirty days after injection the electroretinographic responses had recovered, except in the eyes injected with 20 micrograms TGF-beta(1), which still showed a decrease in step 1. Histological examination of paraffin sections did not demonstrate significant change. Corneal thickness of the eyes receiving 20 micrograms TGF-beta(1) was twice that of the normal cornea and some corneal endothelial cells lost their hexagonal shape. TGF-beta(1) injected intravitreally at doses > or = 1 micrograms is toxic to the cornea. Retinal function is only slightly disturbed by 20 micrograms of TGF-beta(1).


RBE of quasi-monoenergetic 60 MeV neutron radiation for induction of dicentric chromosomes in human lymphocytes.
The production of dicentric chromosomes in human lymphocytes by high-energy neutron radiation was studied using a quasi-monoenergetic 60 MeV neutron beam. The average yield coefficient [see text] of the linear dose-response relationship for dicentric chromosomes was measured to be (0.146+/-0.016) Gy-1. This confirms our earlier observations that above 400 keV, the yield of dicentric chromosomes decreases with increasing neutron energy. Using the linear-quadratic dose-response relationship for dicentric chromosomes established in blood of the same donor for 60Co gamma-rays as a reference radiation, an average maximum low-dose RBE (RBEM) of 14+/-4 for 60 MeV quasi-monoenergetic neutrons with a dose-weighted average energy [see text] of 41.0 MeV is obtained. A correction procedure was applied, to account for the low-energy continuum of the quasi-monoenergetic spectral neutron distribution, and the yield coefficient alpha for 60 MeV neutrons was determined from the measured average yield coefficient [see text]. For alpha, a value of (0.115+/-0.026) Gy-1 was obtained corresponding to an RBEM of 11+/-4. The present experiments extend earlier investigations with monoenergetic neutrons to higher energies.


Starch Digestion by Gut Bacteria: Crowdsourcing for Carbs.
Starch is a polymer of glucose and is one of the most abundant carbohydrates in a Western diet. Resistant starch escapes digestion by host small intestinal glucoamylases and transits the colon where it is degraded by the combined efforts of many gut bacteria. Bacterial metabolism and fermentation of resistant starch leads to increases in short-chain fatty acids, including the clinically beneficial butyrate. Here, we review the molecular machinery that gut bacteria use to degrade starch and how these functions may intersect to facilitate complete starch digestion. While the protein complexes that gut bacteria use to degrade starch differ across phyla, some molecular details converge to promote the optimal positioning of enzymes and substrate for starch degradation.


Chronic myelogenous leukemia in the course of chronic lymphocytic leukemia: evidence for an independent clonal origin.
We report on a 69-year-old man who developed Ph-positive CML 6 years after the onset of B-cell CLL. When CML was diagnosed, both malignant cell populations were detected in bone marrow and peripheral blood. Peripheral leukocytes were fractionated by Ficoll-Hypaque density gradient, and cytogenetic and molecular studies were performed on mononuclear cell and granulocyte-enriched populations. Mononuclear cells were stimulated with either PHA or PWM. In PHA-treated cultures 76% of the metaphases were Ph-negative, while after PWM stimulation 87% were Ph-positive. A bcr rearrangement was observed in DNA from the granulocyte-enriched fraction, but not in mononuclear cells. On the contrary the IgH locus resulted in monoclonally rearranged DNA, only in peripheral blood mononuclear cells. These results indicate that the two neoplastic populations originated independently.


KMT5A Knockdown Suppresses Osteosarcoma Cell Proliferation and Metastasis Through Ꞵ-Catenin Signalling.
Osteosarcoma (OS) is the most common malignant solid bone tumor in children and young adults. We aimed to investigate the effects and cellular mechanisms of KMT5A on OS cell activity. The protein expression was evaluated in the clinical normal, adjacent and OS osteogenic tissues. Knockdown of KMT5A was achieved by KMT5A siRNAs in a human OS cell line, MG63, to detect cell proliferation and metastasis. KMT5A expression was upregulated in clinical OS tissues. Knockdown of KMT5A inhibited cell proliferation but enhanced cell death, with significantly reduced cyclinD1 and Bcl2 and increased cleaved-caspase9 levels. KMT5A knockdown also suppressed OS cell migration and invasion capacity and deceased MMP3 and vimentin expression. β-catenin levels were upregulated in OS tissues and blocking KMT5A resulted in a significant decline in β-catenin expression in the OS cells. Further administration of β-catenin activator remarkably increased protein levels of KMT5A, cyclinD1, Bcl2, MMP3, and vimentin, which showed reversed effects of KMT5A knockdown on OS cell activity. KMT5A knockdown plays an inhibitory role in OS cell proliferation and metastasis through β-catenin signalling, which provides basic evidence and suggests potential targets for OS therapeutic research.


Continuous monitoring of brain perfusion by cerebral oximetry after spontaneous return of circulation in cardiac arrest: a case report.
Cerebral resuscitation determines the prognosis for patients who have experienced sudden death, and brain protection is the focus of clinical treatment. Cerebral resuscitation depends on the timing and quality of cardiopulmonary resuscitation (CPR). At present, cerebral oxygen monitoring is used mainly to monitor the quality of external cardiac compression and provide a prognosis for the nervous system. However, after the return of autonomous circulation, it is necessary to conduct continuous monitoring to ensure measures are taken timeously since hemodynamic instability, brain edema, and other factors may cause occult brain injury, and invasive arterial pressure cannot represent cerebral perfusion. By using continuous cerebral oxygen monitoring after CPR and the return of spontaneous circulation, a patient who was witnessed to have experienced sudden death in the hospital was found to have insufficient cerebral perfusion; he underwent timely intra-aortic balloon counterpulsation to improve his hemodynamics and cerebral perfusion. The patient went on to achieve a good neurological prognosis. Cerebral oxygen monitoring should be conducted throughout the treatment period; physicians should understand cerebral perfusion in real time and implement timely intervention measures to reduce occult brain injury and improve the neurological prognosis of patients.


Enhanced photocatalytic performance of heterogeneous hydrotalcite by spontaneously polarized ferroelectric.
Two-dimensional photocatalytic materials have attracted great attention due to their large specific surface area and abundant active sites. Suppressing the recombination of photo-excited carriers is an effective approach to improve the performances of photocatalytic materials. Herein, we introduced ferroelectric PbTiO3 into the two-dimensional layered double hydroxides (LDHs) to improve the carrier separation efficiency and photocatalytic performances. A built-in electric field was generated in the polarized PbTiO3, resulting in the improvement of the carrier separation efficiency and the promotion of the lifetime of photo-excited carriers in the LDHs-PbTiO3 composites. As a result, the LDHs-PbTiO3 composites showed the decent photocatalytic performances towards water splitting under visible light irradiation. The oxygen production rate of the proposed LDHs-PbTiO3 composites was almost twice than that of pristine LDHs. These results have addressed the significance of photo-excited carriers in photocatalytic materials. This approach could undoubtedly provide the valuable information in design and construction of high efficiency photocatalysts.


T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.
We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.


Outpatient management of preterm prelabor rupture of membranes before 34 weeks: Maternal and neonatal outcomes.
To evaluate the maternal, fetal, and neonatal outcomes of pregnant women complicated with preterm prelabor rupture of membranes (PPROM) eligible for outpatient care. This study included a retrospective cohort of patients with singleton pregnancies with PPROM between 23+0 to 34+0 weeks who remained pregnant after the first 72 h. Outpatient management was considered in women with clinical, ultrasound and analytical stability, and easy access to hospital. Maternal, fetal, and neonatal results were compared between women managed as inpatients versus those managed as outpatients. Women eligible for the outpatient management had a better prognostic profile (no anhydramnios, longer cervical length, less intraamniotic infection, and clinical, ultrasound, and analytical stability) and presented a lower gestational age at admission and longer latency to delivery, resulting in a similar gestational age at delivery as the inpatient group. Postpartum curettage, uterine atony, respiratory distress syndrome, and bronchopulmonary dysplasia were less frequent in the outpatient group. Composite maternal-fetal morbidity and mortality outcomes were similar in both groups, while composite neonatal morbidity and mortality outcomes were significantly lower in the outpatient group. Outpatient management may be an option for women presenting stable PPROM before 34 weeks when adequate selection criteria are fulfilled. Differences in perinatal outcomes in the outpatient group compared with the inpatient group are probably attributable to baseline characteristics. Further prospective randomized studies are needed to confirm the benefits of outpatient management in PPROM.


The RecJ2 protein in the thermophilic archaeon Thermoplasma acidophilum is a 3'-5' exonuclease that associates with a DNA replication complex.
RecJ/cell division cycle 45 (Cdc45) proteins are widely conserved in the three domains of life, i.e. in bacteria, Eukarya, and Archaea. Bacterial RecJ is a 5'-3' exonuclease and functions in DNA repair pathways by using its 5'-3' exonuclease activity. Eukaryotic Cdc45 has no identified enzymatic activity but participates in the CMG complex, so named because it is composed of Cdc45, minichromosome maintenance protein complex (MCM) proteins 2-7, and GINS complex proteins (Sld5, Psf11-3). Eukaryotic Cdc45 and bacterial/archaeal RecJ share similar amino acid sequences and are considered functional counterparts. In Archaea, a RecJ homolog in Thermococcus kodakarensis was shown to associate with GINS and accelerate its nuclease activity and was, therefore, designated GAN (GINS-associated nuclease); however, to date, no archaeal RecJ·MCM·GINS complex has been isolated. The thermophilic archaeon Thermoplasma acidophilum has two RecJ-like proteins, designated TaRecJ1 and TaRecJ2. TaRecJ1 exhibited DNA-specific 5'-3' exonuclease activity, whereas TaRecJ2 had 3'-5' exonuclease activity and preferred RNA over DNA. TaRecJ2, but not TaRecJ1, formed a stable complex with TaGINS in a 2:1 molar ratio. Furthermore, the TaRecJ2·TaGINS complex stimulated activity of TaMCM (T. acidophilum MCM) helicase in vitro, and the TaRecJ2·TaMCM·TaGINS complex was also observed in vivo However, TaRecJ2 did not interact with TaMCM directly and was not required for the helicase activation in vitro These findings suggest that the function of archaeal RecJ in DNA replication evolved divergently from Cdc45 despite conservation of the CMG-like complex formation between Archaea and Eukarya.


Porokeratosis [correction of Parakeratosis] Mibelli and skin carcinoma: a critical review.
The literature on porokeratosis [corrected] Mibelli (PM) is revised critically with respect to the development of skin carcinoma. The incidence of epidermal malignancies in PM lesions is 7% (17 of 250 cases). An influence of X-ray treatment is not excluded in 4 cases with tumors in PM.


Therapeutic options in hepatocellular carcinoma: a comprehensive review.
Hepatocellular carcinoma (HCC) is a chronic liver disease that is highly fatal if not detected and treated early. The incidence and death rate of HCC have been increasing in recent decades despite the measures taken for preventive screening and effective diagnostic and treatment strategies. The pathophysiology of HCC is multifactorial and highly complex owing to its molecular and immune heterogeneity, and thus the gap in knowledge still precludes making choices between viable therapeutic options and also the development of effective regimens. The treatment of HCC demands multidisciplinary approaches and primarily depends on tumor stage, hepatic functional reserve, and response to treatment by patients. Although curative treatments are limited but critical in the early stages of cancer, there are numerous palliative treatments available for patients with intermediate and advanced-stage HCC. In recent times, the use of combination therapy has succeeded over the use of monotherapy in the treatment of HCC by achieving effective tumor suppression, increasing survival rate, decreasing toxicity, and also aiding in overcoming drug resistance. This work focuses on reviewing the current and emerging treatment strategies for HCC.


[Molecular genotyping in refractory thyroid cancers in 2021: When, how and why? A review from the TUTHYREF network].
Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting.


Leukocyte oxidant and antioxidant status in asthmatic patients.
Oxidative stress mediated by reactive oxygen species (ROS) is recognized to contribute significantly to the inflammatory process of bronchial asthma (BA). These species are released into the airway by activated inflammatory cells such as leukocytes. In this study, we aimed to determine whether the oxidant-antioxidant balance is changed in leukocytes of patients with BA. Thirty eight patients (21 male, 17 female) aged 22-68 years and controls of 32 subjects (18 male, 14 female) aged 20-63 years were included in the study. A total of 10 mL venous blood was drawn, leukocytes were separated and lipid peroxidation (LPO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and vitamin C levels were determined in both patients and controls. Leukocyte LPO and SOD activity in the patient group were higher than that of controls (p <0.001 and p <0.05, respectively). However, leukocyte GSH-Px and vitamin C levels in the patient group were lower than that of controls (p <0.01 and p <0.001, respectively). The results suggest that there are alterations in a wide array of oxidants and antioxidants with balance shifting toward increased oxidative stress in BA.


Cross sectional study on proportion of sulfonylureas among various oral antidiabetic drugs using for Japanese patients with type 2 diabetes, analyzed from NSAID Study-2.
We aimed to investigate the certainty of using sulfonylureas in Japanese patients with type 2 diabetes mellitus (T2DM) by analyzing data from the 2018 Nationwide Survey on Actual Intervention for T2DM by Japanese Practitioners (NSAID Study). Of the 6525 and 1545 participants in the NSAID Study under the care of general practitioners (GP) and diabetes specialists (SP), respectively, we included 5423 (83.1%) and 1058 (68.5%) patients who were treated with only oral antidiabetic drugs (OADs) by GPs and SPs, respectively, in the analysis. Among the seven OAD classes in monotherapy, sulfonylureas were the third and fifth most prescribed OADs by GPs (7.1%) and SPs (6.4%), respectively. Sulfonylurea usage increased with combination therapy. Glimepiride was the most commonly prescribed sulfonylurea. Patients who used sulfonylureas had higher hemoglobin A1c (HbA1c) levels and lower body mass indices (BMIs) than patients who did not use sulfonylureas. The results of this study clearly demonstrated that, among the OADs, sulfonylureas were not frequently used in monotherapy, although the opportunity of using sulfonylurea increased with the number of OADs prescribed in combination therapies by both GPs and SPs in Japan. Moreover, low-dose glimepiride was the most-prescribed sulfonylurea for Japanese T2DM patients, especially for those who were lean and had higher HbA1c levels.


Impact of clonal lineages on susceptibility of Staphylococcus lugdunensis to chlorhexidine digluconate and chloride benzalkonium.
Little is known about susceptibility of Staphylococcus lugdunensis to antiseptics. The objective of this study was to evaluate, at the molecular and phenotypic level, the susceptibility of 49 clinical S. lugdunensis strains (belonging to the seven clonal complexes [CCs] defined by multilocus sequence typing) to two antiseptics frequently used in healthcare settings (chlorhexidine digluconate [CHX] and chloride benzalkonium [BAC]). The minimum inhibitory concentrations (MICs), by broth microdilution method, varied for BAC from 0.25 mg/L to 8 mg/L (MIC50 = 1 mg/L, MIC90 = 2 mg/L) and for CHX from 0.5 mg/L to 2 mg/L (MIC50 = 1 mg/L, MIC90 = 2 mg/L). The BAC and CHX minimum bactericidal concentrations (MBCs) varied from 2 mg/L to 8 mg/L (MBC50 = 4 mg/L, MBC90 = 8 mg/L) and from 2 mg/L to 4 mg/L (MBC50 and MBC90 = 4 mg/L), respectively. A reduced susceptibility to CHX (MIC = 2 mg/L) was observed for 12.2% of the strains and that to BAC (MIC ≥ 4 mg/L) for 4.1%. The norA resistance gene was detected in all the 49 isolates, whereas the qacA gene was rarely encountered (two strains; 4.1%). The qacC, qacG, qacH, and qacJ genes were not detected. The two strains harboring the qacA gene had reduced susceptibility to both antiseptics and belonged to CC3. The norA gene was detected in all the strains, suggesting that it could belong to the core genome of S. lugdunensis. S. lugdunensis is highly susceptible to both antiseptics tested. Reduced susceptibility to BAC and CHX was a rare phenomenon. Of note, a tendency to higher MICs of BAC was detected for CC3 isolates. These results should be confirmed on a larger collection of strains.


Risk aversion connectedness in developed and emerging equity markets before and after the COVID-19 pandemic.
This study investigates the dynamic connectedness across the variance risk premium in international developed and emerging equity markets based on a Bayesian time-varying parameter vector autoregressive methodology. The empirical results indicate that the total spillover index is on average 65.6%, indicating a high, albeit declining, level of interconnectedness across the investor sentiment in the three markets under review until early 2020. Following the COVID-19 outbreak though, the total investors' risk aversion connectedness - as expected - strengthens, but more importantly, its dynamics alter, indicating that the risk aversion of emerging markets is an important contributor to the connectedness of international markets.


The future pediatrician: the challenge of chronic illness.
To relate the changing epidemiology of childhood to current patterns of pediatric practice in the United States, a critical literature review and selected analyses of national datasets, including the National Health Interview Survey, the National Hospital Discharge Survey, and National Vital Statistics System, were conducted. Trends over the past several decades suggest that the incidence of serious acute illness in children has fallen while the prevalence of chronic disease has risen. These trends have resulted in a growing concentration of serious childhood morbidity and mortality into chronic disorders. Current pediatric practice structures appear to be poorly suited to meet the growing demands of chronic disease in children and likely will require major reform in organization, financing, and training.


True thymic hyperplasia associated with severe thymic cyst bleeding in a newborn: case report and review of the literature.
We report on a 5-week-old male infant with recurrent respiratory distress since birth and congenital thymic hyperplasia. Acute life-threatening thymic bleeding apparently from ruptured thymic cysts into the pleural spaces complicated the clinical situation. Thoracotomy and complete thymectomy were performed. Histologic examination revealed normal thymic architecture with cysts of different sizes and an increased thymic weight of 30 g. The combination of true thymic hyperplasia and cyst bleeding in a newborn has not been previously reported and will be discussed in relation to the available literature on respiratory distress due to thymic pathology in childhood.


Sudden unexpected death following exercise and congenital anomalies of coronary arteries. A report of two cases.
Two cases of anomalous origin of the left coronary artery from the pulmonary trunk with unusually prolonged post-childhood survival are presented. In both cases, death was associated with physical exertion. The pathological findings included enlarged right coronary ostium, myocardial hypertrophy, endocardial fibrosis, and focal myocardial scarring.


A Review of Quality Assurance Methods to Assist Professional Record Keeping: Implications for Providers of Interpersonal Violence Treatment.
Errors have been found to frequently occur in the management of case records within mental health service systems. In cases involving interpersonal violence, such errors have been found to negatively impact service implementation and lead to significant trauma and fatalities. In an effort to ensure adherence to specified standards of care, quality assurance programs (QA) have been developed to monitor and enhance service implementation. These programs have generally been successful in facilitating record management. However, these systems are rarely disseminated, and not well integrated. Therefore, within the context of interpersonal violence, we provide an extensive review of evidence supported record keeping practices, and methods to assist in assuring these practices are implemented with adherence.


Origins of the spontaneous receptor potential in the tuberous organ in a mormyrid fish.
In an electroreceptor of a Mormyrid fish: 1. The correlations between the number of sensory cells in each receptor organ and the mode of the intervals of time between receptor potentials are not significant within the temperature ranges of 20.0-26.0 degrees C, 20.5-21.5 degrees C, 22.0-23.0 degrees C and are significant at a level of 4.9% within 25.0-26.0 degrees C. 2. The correlations between the mode of intervals of time between receptor potentials and temperature are significant at a level inferior to 1% for isolated receptor organs and also at a level of 5.8% for 21 different receptor organs from 9 different fishes.


In Vitro Human Gastrointestinal Tract Simulation Systems: A Panoramic Review.
Simulated human gastrointestinal (GI) tract systems are important for their applications in the fields of probiotics, nutrition and health. To date, various in vitro gut systems have been available to study GI tract dynamics and its association with health. In contrast to in vivo investigations, which are constrained by ethical considerations, in vitro models have several benefits despite the challenges involved in mimicking the GI environment. These in vitro models can be used for a range of research, from simple to dynamic, with one compartment to several compartments. In this review, we present a panoramic development of in vitro GI models for the first time through an evolutionary timeline. We tried to provide insight on designing an in vitro gut model, especially for novices. Latest developments and scope for improvement based on the limitations of the existing models were highlighted. In conclusion, designing an in vitro GI model suitable for a particular application is a multifaceted task. The bio-mimicking of the GI tract specific to geometrical, anatomical and mechanical features remains a challenge for the development of effective in vitro GI models. Advances in computer technology, artificial intelligence and nanotechnology are going to be revolutionary for further development. Besides this, in silico high-throughput technologies and miniaturisation are key players in the success of making in vitro modelling cost-effective and reducing the burden of in vivo studies.


Development and clinical evaluation of a three-dimensional cone-beam computed tomography estimation method using a deformation field map.
To develop a three-dimensional (3D) cone-beam computed tomography (CBCT) estimation method using a deformation field map, and to evaluate and optimize the efficiency and accuracy of the method for use in the clinical setting. We propose a method to estimate patient CBCT images using prior information and a deformation model. Patients' previous CBCT data are used as the prior information, and the new CBCT volume to be estimated is considered as a deformation of the prior image volume. The deformation field map is solved by minimizing deformation energy and maintaining new projection data fidelity using a nonlinear conjugate gradient method. This method was implemented in 3D form using hardware acceleration and multi-resolution scheme, and it was evaluated for different scan angles, projection numbers, and scan directions using liver, lung, and prostate cancer patient data. The accuracy of the estimation was evaluated by comparing the organ volume difference and the similarity between estimated CBCT and the CBCT reconstructed from fully sampled projections. Results showed that scan direction and number of projections do not have significant effects on the CBCT estimation accuracy. The total scan angle is the dominant factor affecting the accuracy of the CBCT estimation algorithm. Larger scan angles yield better estimation accuracy than smaller scan angles. Lung cancer patient data showed that the estimation error of the 3D lung tumor volume was reduced from 13.3% to 4.3% when the scan angle was increased from 60° to 360° using 57 projections. The proposed estimation method is applicable for 3D DTS, 3D CBCT, four-dimensional CBCT, and four-dimensional DTS image estimation. This method has the potential for significantly reducing the imaging dose and improving the image quality by removing the organ distortion artifacts and streak artifacts shown in images reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm.


The genetics of obsessive compulsive disorder and Gilles de la Tourette's syndrome.
This article reviews the evidence that obsessive compulsive disorder (OCD) and Gilles de la Tourette's syndrome (GTS) are both familial and genetic. Studies are summarized that suggest that (1) some forms of OCD are related to GTS, (2) some forms of OCD are familial and may not be related to GTS, and (3) the patterns of inheritance of GTS and OCD within the same families are consistent with the transmission of an autosomal dominant genetic locus.


Does the Anionic Surfactant Isopropylamine Dodecylbenzene Sulfonate Induce Hepatic Oxidative Stress and Impairment in Carassius auratus gibelio?
Isopropylamine dodecylbenzene sulfonate (IDS) is a new kind of anionic surfactant (ANS). To preliminarily evaluate the aquatic toxicity of IDS, this study took gibel carp (Carassius auratus gibelio) as the research object. The well-acclimatized fish were divided into six groups and exposed to 0 mg/L, 0.5 mg/L, 1.0 mg/L, 2.0 mg/L, 4.0 mg/L, or 8.0 mg/L of IDS for 7, 14, 21 or 28 days. Our results showed that the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the liver were unaffected by IDS exposure, while glutathione peroxidase (GSH-Px) activity was significantly inhibited. Hepatic tissue exhibited pathological damage, characterized by nuclear migration and dissolution and cell boundary blurring. The results suggest that IDS does not cause oxidative stress in the liver, but cause hepatic histopathological damage. GSH-Px can be considered as a biomarker of IDS exposure in gibel carp.


Expression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reproducibility for in vitro phenotyping studies.
Primary human hepatocytes are an essential in vitro tool for evaluating drug metabolism, drug-drug interactions, and hepatotoxicity. This model is considered as the gold standard in matter of DMPK studies in both industrial and academic research. The primary human hepatocytes are used either in suspension or in monolayer, as fresh or frozen cells. However, the use of this model is limited due to the lack of availability, rapid loss of functionality, high cost as well as the variable hepatocyte plating efficiencies in culture and the limited stock of hepatocytes derived from the same origin. Chimeric TK-NOG mice with humanized livers (humanized liver mice) are an attractive platform for drug metabolism and toxicity, which were produced by transplanting human hepatocytes into immunodeficient mice with injured livers. Here, we show that, using humanized mouse liver, in vivo human hepatocyte repopulation was over ~100-fold enabling the continuous and abundant use of human hepatocytes of the same origin and improving their plateability. In our latest cell preparations, hepatocytes isolated from humanized liver mice (Hu-Liver cells) exhibited high purity (ratio of HLA-positive cells: 92±3%), good viability (75±12%), and yield (1.0×108 cells/mouse). Human hepatic drug metabolizing enzymes, transporters, and nuclear receptors genes were expressed in humanized mouse liver. Drug-metabolizing activities in Hu-Liver cells were comparable to or higher than those in primary human hepatocytes. An extensive P450-dependent human drug metabolism was observed in Hu-Liver cells. CYP1A2, CYP2B6, and CYP3A4/5 activities/mRNA in Hu-Liver cells were induced by the hepatocyte exposure to typical human P450 inducers, omeprazole, phenobarbital, and rifampicin, respectively. Finally, Human albumin secretion and CYP3A-mediated drug oxidation activity were maintained over 4-weeks. Altogether, the expression level of pharmacokinetics-related genes, enzyme activity, human-typed drug metabolism, and inducibility of P450 in Hu-Liver cells make from humanized mouse liver a relevant and robust model for in vitro preclinical studies, including drug metabolism, pharmacokinetics, and toxicology studies.


Gender differences in asthma development and progression.
Asthma is a chronic inflammatory airway disease that has a higher prevalence in boys than in girls before puberty and a higher prevalence in women than in men in adulthood. Because of the complexity of the disease, no single straightforward mechanism can explain the gender differences found in asthma. This article reviews the effects of sex on the development and outcome of atopy and asthma. English-language articles were identified by a PubMed database search from 1980 to 2007 using the terms asthma, gender, sex, hormones, and lung development. It is likely that hormonal changes and genetic susceptibility both contribute to the change in prevalence that occurs about the time of puberty. Severe asthma is also more predominant in females. In adulthood, women are more susceptible to the effects of smoking and more likely to develop asthma. It is important to determine whether asthma is a social, cultural, hormonal, and/or genetic issue. A number of topics on gender differences in asthma development and progression require additional research. For example, the interaction of fetal lung development and hormonal factors needs to be studied because it has consequences throughout life. Genetic studies of asthma should be stratified by sex, because some polymorphisms are particularly related to asthma in females. Further studies should be conducted on hormone-gene interactions (eg, X-chromosome genes) in relation to asthma and atopy. In addition, cellular hormonal influences in asthma and atopy in relation to innate and acquired immunity in both sexes need to be examined. This would benefit patients not only with asthma but also with many other diseases that show gender differences in prevalence, severity, and treatment response. Animal models investigating observed gender differences in humans should focus on susceptibility to environmental and hormonal factors in relation to lung and immune development. Differences in treatment response in asthma need to be examined as well. Double-blind studies need to be stratified by sex, and treatment responses in females and males should be investigated separately. Furthermore, interaction between gender and behavioral change in relation to asthma development and management should be studied.


Area under the curve predictions of dalbavancin, a new lipoglycopeptide agent, using the end of intravenous infusion concentration data point by regression analyses such as linear, log-linear and power models.
1. Dalbavancin, a lipoglycopeptide, is approved for treating gram-positive bacterial infections. Area under plasma concentration versus time curve (AUCinf) of dalbavancin is a key parameter and AUCinf/MIC ratio is a critical pharmacodynamic marker. 2. Using end of intravenous infusion concentration (i.e. Cmax) Cmax versus AUCinf relationship for dalbavancin was established by regression analyses (i.e. linear, log-log, log-linear and power models) using 21 pairs of subject data. 3. The predictions of the AUCinf were performed using published Cmax data by application of regression equations. The quotient of observed/predicted values rendered fold difference. The mean absolute error (MAE)/root mean square error (RMSE) and correlation coefficient (r) were used in the assessment. 4. MAE and RMSE values for the various models were comparable. The Cmax versus AUCinf exhibited excellent correlation (r > 0.9488). The internal data evaluation showed narrow confinement (0.84-1.14-fold difference) with a RMSE < 10.3%. The external data evaluation showed that the models predicted AUCinf with a RMSE of 3.02-27.46% with fold difference largely contained within 0.64-1.48. 5. Regardless of the regression models, a single time point strategy of using Cmax (i.e. end of 30-min infusion) is amenable as a prospective tool for predicting AUCinf of dalbavancin in patients.


Most published systematic reviews of remdesivir for COVID-19 were redundant and lacked currency.
To investigate the completeness and currency of published systematic reviews of remdesivir for COVID-19 and to compare this with a living guidelines approach. In this cross-sectional study, we searched Europe PMC on May 20, 2021 for systematic reviews of remdesivir (including preprints, living review updates). Completeness and currency were based on the inclusion of four major randomized trials of remdesivir available at the time of publication of the review (including as preliminary results and preprints). We included 38 reviews (45 reports), equivalent to a new publication every 9 days. 23 (51%) reports were out of date at the time of publication. Eleven reviews that were current on publication had a median survival time of 10 days (range 4-57). A third of reviews cited other systematic reviews, but only four provided justifications for why another review was necessary. Eight (21%) of the reviews were registered in PROSPERO. The Australian COVID-19 Clinical Evidence Taskforce living guidelines were updated within 14 days for three of the remdesivir trials, and within 28 days for the fourth. There was considerable duplication of systematic reviews of remdesivir, and half were already out of date at the time of publication.


Computerized tomography (CT) in otolaryngology.
Computerized tomography (CT) of the brain has been available since 1973 and has changed neurological, neurosurgical and radiological practice beyond recognition. A rapid growth of literature has documented it role in the diagnosis of intracranial hematoma, cerebral atrophy, brain tumor, orbital lesions and postoperative tumor evaluation. This computerized method of image reconstruction is now also being applied to the rest of the body and to other diagnostic modalities such as isotopes and ultrasound. The initial impact of CT scanning in otolaryngology is largely in four areas: 1. Facial deformities either acquired or congenital as hypertelorism, fibrous dysplasia, ossifying fibroma and Crouzon's disease. 2. Tumors involving sinuses primarily or by secondary invasion. 3. Cerebello-pontine angle lesions as meningiomas, acoustic neuromas, and glomus jugulare tumors. The larger acoustic neuroma is well visualized by this technique rendering contrast myelography unnecessary. In CT scanning, subtle differences in position and an increase in density before contrast enhancement should allow a differentiation of angle meningiomas from acoustic neuromas; in addition, CT scanning has a very important role in the postoperative assessment of angle tumors. 4. Infections as cerebral abscess or cerebritis secondary to sinus or mastoid disease. The future holds changes that will allow much finer detail, re-orientation of the horizontal information into any plane, and much more accurate differentiation of tissue density. The principle of CT image reconstruction is being applied to both isotope and ultrasound scanning and should improve their accuracy and yield. If the rapid growth of the new technology over the past two years continues, even greater usefulness can be anticipated.


Multiple Intracranial Aneurysms Caused by Myxoma: Case Report and Literature Review.
We present a case of multiple myxoma-related intracranial aneurysms and reviewed the recent relevant literature to investigate their natural course and develop a reasonable treatment algorithm. We have reported a new case of multiple myxoma-related intracranial aneurysms and performed a search of current studies (2001 to the present) in PubMed. The keywords used were as follows (single words or combinations): neoplastic aneurysm, oncotic aneurysm, aneurysm, and myxoma. Only patients with multiple aneurysms resulting from cardiac myxoma and with adequate follow-up information pertinent to the analysis were included. A total of 41 patients, including our present patient, were studied. Of the 41 patients, 28 had received conservative treatment as the primary choice. Most lesions (n = 22) were stable during follow-up, except for 3 in which aneurysm evolution was observed. A total of 8 patients had undergone microsurgery, including aneurysm resection in 3, aneurysm clipping in 2, clipping followed by resection in 2, and aneurysm trapping in 1. Endovascular treatment was performed in 2 patients. Radiation therapy was used in 1 patient, and the parent artery proved to be occluded at the 1-year follow-up examination. A combination of chemotherapy and microsurgery was used in 1 patient. All the cases that had been managed aggressively were stable during further follow-up. The prognosis was good for most patients with multiple myxoma-related intracranial aneurysms, and most myxoma-related aneurysms were stable. Conservative treatment and routine follow-up are recommended for most patients. However, for patients with evolving or ruptured aneurysms, invasive treatment, including open surgery and endovascular treatment, should be considered.


Delta/Notch signaling promotes formation of zebrafish neural crest by repressing Neurogenin 1 function.
In zebrafish, cells at the lateral edge of the neural plate become Rohon-Beard primary sensory neurons or neural crest. Delta/Notch signaling is required for neural crest formation. ngn1 is expressed in primary neurons; inhibiting Ngn1 activity prevents Rohon-Beard cell formation but not formation of other primary neurons. Reducing Ngn1 activity in embryos lacking Delta/Notch signaling restores neural crest formation, indicating Delta/Notch signaling inhibits neurogenesis without actively promoting neural crest. Ngn1 activity is also required for later development of dorsal root ganglion sensory neurons; however, Rohon-Beard neurons and dorsal root ganglion neurons are not necessarily derived from the same precursor cell. We propose that temporally distinct episodes of Ngn1 activity in the same precursor population specify these two different types of sensory neurons.


Envelopment by endothelial cells initiates translocation of avian primordial germ cell into vascular tissue.
In avian species, primordial germ cells (PGCs) migrate to the gonadal primordium through the vascular system. Because this mode of migration is reminiscent of cancer metastasis, it would be useful to elucidate the mechanisms underlying PGC migration via the bloodstream. Here, we sought to determine when, where, and how PGCs enter the vascular network by double visualization of PGCs and endothelial cells (ECs) in tie1:H2B-eYFP transgenic quails. In the left and right lateral germinal crescent regions corresponding to the anterior-most area vasculosa, more than 60% of PGCs were enveloped by differentiating ECs forming blood islands prior to vascular network formation. Cell morphology analysis suggested that the PGC-EC interaction was instructed by differentiating ECs. At a later developmental stage, ECs anastomosed to form a vascular network with a lumen that retained PGCs within it. As a consequence, many PGCs localized within the luminal space of the mature vascular network at later stages. Our findings demonstrate that the major type of avian PGC translocation into vascular tissue is not a typical intravasation, as performed by types of metastatic cancer cells, but rather a passive translocation (envelopment) mediated by differentiating ECs during early vasculogenesis.


The biological underpinnings of therapeutic resistance in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality in the United States and has only recently achieved a 5-yr survival rate of 10%. This dismal prognosis reflects the remarkable capacity of PDAC to effectively adapt to and resist therapeutic intervention. In this review, we discuss recent advances in our understanding of the biological underpinnings of PDAC and their implications as targetable vulnerabilities in this highly lethal disease.


Establishing a distributed campus: making sense of disruptions to a doctor community.
In August 2004, the Northern Medical Program (NMP), a distributed campus of the Faculty of Medicine at the University of British Columbia, Canada, admitted its first students. Situated at the University of Northern British Columbia in Prince George, the NMP created new opportunities, challenges, stresses and changes for the approximately 180 local specialists and family doctors. This study examines the initial impacts of the NMP on doctors practising in its host community. Qualitative interview methods were used. A purposive sample was drawn from: (i) doctors who had involvement with the NMP, and (ii) doctors who were not involved with the NMP. Data were collected from May to September 2007 using a semi-structured interview guide. Interviews were audiotaped, transcribed and checked by participants. Analysis involved identifying, coding and categorising key emergent themes until saturation. Prior to the implementation of the NMP, doctors in Prince George had formed cohesive networks, in the face of adverse conditions, that functioned effectively as a form of social capital. The introduction of new doctors and resources through the NMP disrupted this sense of community cohesiveness. Over time, however, the NMP has created new mechanisms by which doctors interact and develop partnerships. The study confirms the value of a social capital framework for understanding a medical community's adaptation to change. At this early point, it appears the NMP has created new mechanisms by which doctors can interact and develop the partnerships and relationships necessary to renew a sense of community cohesion.


Influence of initial pH on thermophilic anaerobic co-digestion of swine manure and maize stalk.
The contradictions between the increasing energy demand and decreasing fossil fuels are making the use of renewable energy the key to the sustainable development of energy in the future. Biogas, a renewable clean energy, can be obtained by the anaerobic fermentation of manure waste and agricultural straw. This study examined the initial pH value had obvious effect on methane production and the process in the thermophilic anaerobic co-digestion. Five different initial pH levels with three different manure ratios were tested. All digesters in different initial pH showed a diverse methane production after 35 days. The VFA/alkalinity ratio of the optimum reaction condition for methanogens activity was in the range of 0.1-0.3 and the optimal condition that at the 70% dung ratio and initial pH 6.81, was expected to achieve maximum total biogas production (146.32 mL/g VS).


Angiogenesis in colorectal cancer.
Angiogenesis is a complicated multistep process involving the breakdown of the endothelial cell basement membrane, digestion of the extracellular matrix, proliferation and migration of endothelial cells toward the angiogenic stimulus, and formation of functioning capillaries. This neovascular network not only provides nutrients for an expanding tumor mass but also a means of dissemination to sites far removed from the primary tumor site. The entire process is mediated by cytokines or growth factors released either by the tumor cells themselves or by endogenous cells within the microenvironment surrounding the tumor. The literature has conclusively shown that those lesions with high angiogenesis scores or microvessel densities are associated with a higher risk of metastases, recurrence, and early patient death. This is especially so for colorectal cancer. Antiangiogenesis therapy holds promise for the future and, in the adjuvant setting, has many theoretical advantages over conventional cytotoxic chemotherapy.


A liquid chromatographic method for determination of acetamiprid and buprofezin residues and their dissipation kinetics in paddy matrices and soil.
The present study was conducted to investigate the residue status of two insecticides (acetamiprid and buprofezin) and their dissipation kinetics in three matrices viz. paddy grain, straw, and soil. The extraction procedure for residues of these two insecticides was executed using acetonitrile solvent. The analytical method was validated, which showed good linearity with the limit of quantification (LOQ) value of 0.01 and 0.02 mg kg-1 for acetamiprid and buprofezin, respectively. The recovery range was 79.67-98.33 % concerning all the matrices in both the insecticides. Acetamiprid (20% SP) and Buprofezin (25% SC) were applied separately in the paddy field in two doses: single dose (recommended dose) and double dose along with untreated control throughout the experiment. Residue analysis of these two insecticides in paddy (grain and straw) and soil was accomplished employing high-performance liquid chromatography (HPLC) with ultraviolet (UV) detector and confirmed by ultra-performance liquid chromatography (UPLC) coupled with mass spectrometry (UPLC-MS/MS). The dissipation data showed that acetamiprid exhibited higher dissipation in comparison with buprofezin. However, their persistence was found slightly higher in soil. The dissipation dynamics in the rice and soil were discussed with biological half-lives of both the insecticides. Consumer risk assessment study was also made considering its fate to the consumers.


Efficacy of bismuth for antibiotic-resistant Helicobacter pylori strains eradication: A systematic review and meta-analysis.
Antibiotic resistance of Helicobacter pylori (H. pylori) is increasing worldwide, and bismuth quadruple therapy has been recommended as a first-line regimen in many areas. This study aimed to investigate whether bismuth would improve the eradication rate (ER) of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains and how much additional efficacy bismuth could achieve. PubMed, EMBASE, Web of Science, and Cochrane Central databases for randomized controlled trials were systematically searched by two independent reviewers until 15 January 2022. Pooled ERs of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains were compared between bismuth-containing and non-bismuth therapies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Eight studies enrolling 340 individuals were included. The RRs of pooled ERs compared between bismuth-containing and non-bismuth therapies were 1.83 for clarithromycin-resistant strains (95% CI 1.16-2.89, pooled ER: 76.9% vs. 36.6%, p = .009, I2 = 0%), 1.39 for metronidazole-resistant strains (95% CI 1.09-1.78, pooled ER: 86.8% vs. 60.9%, p = .008, I2 = 37%), 2.75 for dual clarithromycin/metronidazole-resistant strains (95% CI 1.01-7.52, pooled ER: 76.9% vs. 18.2%, p = .05, I2 = 0%), and 1.04 for levofloxacin-resistant strains (95% CI 0.56-1.93, pooled ER: 63.4% vs. 54.3%, p = .90; I2 = 60%). Bismuth significantly increased the ERs of clarithromycin-, metronidazole-, and dual-resistant strains by 40%, 26%, and 59%, respectively. Subgroup analysis of treatment duration showed that the significantly higher eradication rate for antibiotic-resistant strains in bismuth-containing therapy than non-bismuth therapy was only observed in 14-day treatment regimens and not in 7-day regimens (p = .02 and .17, respectively). Bismuth was most effective in improving the ERs of dual-resistant H. pylori strains, followed by clarithromycin- and metronidazole-resistant strains. Prolonged treatment duration might effectively improve the efficacy of bismuth in overcoming antibiotic resistance.


Scanning electrochemical microscopy studies of micropatterned copper sulfide (Cu(x)S) thin films fabricated by a wet chemistry method.
Patterned copper sulfide (Cu(x)S) microstructures on Si (1 1 1) wafers were successfully fabricated by a relatively simple solution growth method using copper sulfate, ethylenediaminetetraacetate and sodium thiosulfate aqueous solutions as precursors. The Cu(x)S particles were selectively deposited on a patterned self-assembled monolayer of 3-aminopropyltriethoxysilane regions created by photolithography. To obtain high quality Cu(x)S films, preparative conditions such as concentration, proportion, pH and temperature of the precursor solutions were optimized. Various techniques such as optical microscopy, atomic force microscopy (AFM), X-ray diffraction, optical absorption and scanning electrochemical microscopy (SECM) were employed to examine the topography and properties of the micro-patterned Cu(x)S films. Optical microscopy and AFM results indicated that the Cu(x)S micro-pattern possessed high selectivity and clear edge resolution. From combined X-ray diffraction analysis and optical band gap calculations we conclude that Cu(9)S(5) (digenite) was the main phase within the resultant Cu(x)S film. Both SECM image and cyclic voltammograms confirmed that the Cu(x)S film had good electrical conductivity. Moreover, from SECM approach curve analysis, the apparent electron-transfer rate constant (k) in the micro-pattern of Cu(x)S dominated surface was estimated as 0.04 cm/s. The SECM current map showed high edge acuity of the micro-patterned Cu(x)S.


Human mobility and coronavirus disease 2019 (COVID-19): a negative binomial regression analysis.
This study aimed to examine the link between human mobility and the number of coronavirus disease 2019 (COVID-19)-infected people in countries. Our data set covers 144 countries for which complete data are available. To analyze the link between human mobility and COVID-19-infected people, our study focused on the volume of air travel, the number of airports, and the Schengen system. To analyze the variation in COVID-19-infected people in countries, we used negative binomial regression analysis. Our findings suggest a positive relationship between higher volume of airline passenger traffic carried in a country and higher numbers of patients with COVID-19. We further found that countries which have a higher number of airports are associated with higher number of COVID-19 cases. Schengen countries, countries which have higher population density, and higher percentage of elderly population are also found to be more likely to have more COVID-19 cases than other countries. The article brings a novel insight into the COVID-19 pandemic from a human mobility perspective. Future research should assess the impacts of the scale of sea/bus/car travel on the epidemic. The findings of this article are relevant for public health authorities, community and health service providers, as well as policy-makers.


Computational models of collective behavior.
Computational models of human collective behavior offer promise in providing quantitative and empirically verifiable accounts of how individual decisions lead to the emergence of group-level organizations. Agent-based models (ABMs) describe interactions among individual agents and their environment, and provide a process-oriented alternative to descriptive mathematical models. Recent ABMs provide compelling accounts of group pattern formation, contagion and cooperation, and can be used to predict, manipulate and improve upon collective behavior. ABMs overcome an assumption that underlies much of cognitive science--that the individual is the crucial unit of cognition. The alternative advocated here is that individuals participate in collective organizations that they might not understand or even perceive, and that these organizations affect and are affected by individual behavior.


In vivo confocal microscopy of sub-basal corneal nerves and corneal densitometry after three kinds of refractive procedures for high myopia.
To observe corneal nerve fibers and densitometry after small incision lenticule extraction (SMILE), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and laser-assisted subepithelial keratomileusis (LASEK) for high myopia. This is a prospective, cross-sectional research study. Patients with high myopia (equivalent spherical lens: -6.00 and -11.00D) who underwent laser corneal refractive surgery were divided into three groups: SMILE, FS-LASIK and LASEK. Scheimpflug imaging of corneal nerves in five areas was observed by confocal microscopy before and 6, 12 months after surgery. Corneal densitometry was measured by Pentacam anterior segment analysis system. Overall, 59 patients were enrolled. The nerve density in the central area did not recover to the preoperative level in three groups until 12 months. The density and length of corneal nerves in central and lower area were better in the SMILE group 6 months postoperatively (p = 0.01), while nerve density did not differ significantly among three groups 12 months postoperatively (p = 0.18). Nerve fibers in central and temporal region were wider in LASEK than that in other two groups at 6- and 12-month follow-up. Corneal densitometry in the central 6 mm diameter was significantly higher in the LASEK group compared with other two groups 6 months postoperatively (p = 0.04). Twelve months postoperatively, corneal densitometry in range of all zone was lower in SMILE than in FS-LASIK and LASEK (p = 0.01, 0.03, 0.04). Compared with FS-LASIK and LASEK, SMILE-treated eyes with high myopia had certain advantages in nerve density, length and nerve connection way and had better corneal transparency after operation.


Controlling risk of SARS-CoV-2 infection in essential workers of enclosed food manufacturing facilities.
The SARS-CoV-2 global pandemic poses significant health risks to workers who are essential to maintaining the food supply chain. Using a quantitative risk assessment model, this study characterized the impact of risk reduction strategies for controlling SARS-CoV-2 transmission (droplet, aerosol, fomite-mediated) among front-line workers in a representative enclosed food manufacturing facility. We simulated: 1) individual and cumulative SARS-CoV-2 infection risks from close contact (droplet and aerosols at 1-3m), aerosol, and fomite-mediated exposures to a susceptible worker following exposure to an infected worker during an 8h-shift; and 2) the relative reduction in SARS-CoV-2 infection risk attributed to infection control interventions (physical distancing, mask use, ventilation, surface disinfection, hand hygiene). Without mitigation measures, the SARS-CoV-2 infection risk was largest for close contact (droplet and aerosol) at 1m (0.96, 95%CI: 0.67-1.0). In comparison, risk associated with fomite (0.26, 95%CI: 0.10-0.56) or aerosol exposure alone (0.05, 95%CI: 0.01-0.13) at 1m distance was substantially lower (73-95%). At 1m, droplet transmission predominated over aerosol and fomite-mediated transmission, however, this changed by 3m, with aerosols comprising the majority of the exposure dose. Increasing physical distancing reduced risk by 84% (1 to 2m) and 91% (1 to 3m). Universal mask use reduced infection risk by 52-88%, depending on mask type. Increasing ventilation (from 0.1 to 2-8 air changes/hour) resulted in risk reductions of 14-54% (1m) and 55-85% (2m). Combining these strategies, together with handwashing and surface disinfection, resulted in <1% infection risk. Current industry SARS-CoV-2 risk reduction strategies, particularly when bundled, provide significant protection to essential food workers. Using mathematical modeling, we find that workers in enclosed food manufacturing facilities are at higher risk of SARS-CoV-2 infection from close contact transmission (exposure to large droplets and small aerosol particles) than fomite transmission. Thus, strategies protecting workers should prioritize close contact transmission pathways, such as physical distancing, universal mask use, and room air changes, with surface disinfection (reducing fomite transmission) and handwashing of secondary importance. Our work supports current international (EU-OSHA), domestic (FDA, OSHA), and food industry-standard guidance for managing COVID-19 transmission in essential workers in the food manufacturing sector. Although our model was designed for an indoor food manufacturing setting, it can be readily adapted to other indoor environments and infectious respiratory pathogens.


Supine transgluteal vs prone position in extracorporeal shock wave lithotripsy of distal ureteric stones.
To evaluate of efficacy of transgluteal (supine) approach for shock wave lithotripsy (SWL) in treatment of distal ureteric stones. This prospective, randomized, comparative study was conducted on 98 patients. Patients were randomly assigned into 2 groups: group A (n = 49; prone position) and group B (n = 49; supine position, transgluteal). Inclusion criteria included patients with radiopaque lower ureteric stones ≤10 mm. Exclusion criteria included radiolucent stones, stones >10 mm, the need for any auxiliary procedure, and any contraindication for SWL. Post-SWL evaluation included plain x-ray of kidney, ureter, and bladder at 2 weeks after treatment and then at monthly intervals after treatment for 3 months. Stone-free status was defined as no residual stone fragments visible on plain x-ray. Treatment failure was defined as persistence of stone fragments at 3 months or the need for ureteroscopy. Stone-free rate after 1 treatment session was achieved in 44.9% and 75.5% for prone and supine positions, respectively. Proceeding to ureteroscopy, after failure of the second SWL session to clear the stones, was done in 34.7% and 8.2% for prone and supine positions, respectively. The overall success rate for SWL treatment in prone and supine groups was 65.3% and 91.8%, respectively (P <.001). Transgluteal SWL while patient in supine position proved efficacy for treatment of distal ureteric stones. Larger group studies comparing the results of SWL in supine position with those of prone position and also with those of ureteroscopy may enrich our data to reach a consensus for the ideal management of distal ureteric stones.


Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction.
Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.


Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein.
The vast majority of physiological processes in living cells are mediated by protein-protein interactions often specified by particular protein sequence motifs. PDZ domains, composed of 80-100 amino acid residues, are an important class of interaction motif. Among the PDZ-containing proteins, glutaminase interacting protein (GIP), also known as Tax Interacting Protein TIP-1, is unique in being composed almost exclusively of a single PDZ domain. GIP has important roles in cellular signaling, protein scaffolding and modulation of tumor growth and interacts with a number of physiological partner proteins, including Glutaminase L, β-Catenin, FAS, HTLV-1 Tax, HPV16 E6, Rhotekin and Kir 2.3. To identify the network of proteins that interact with GIP, a human fetal brain cDNA library was screened using a yeast two-hybrid assay with GIP as bait. We identified brain-specific angiogenesis inhibitor 2 (BAI2), a member of the adhesion-G protein-coupled receptors (GPCRs), as a new partner of GIP. BAI2 is expressed primarily in neurons, further expanding GIP cellular functions. The interaction between GIP and the carboxy-terminus of BAI2 was characterized using fluorescence, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy assays. These biophysical analyses support the interaction identified in the yeast two-hybrid assay. This is the first study reporting BAI2 as an interaction partner of GIP.


Prostate cancer metabolite quantification relative to water in 1H-MRSI in vivo at 3 Tesla.
(1)H magnetic resonance spectroscopic imaging was performed on 16 men with suspected prostate cancer using an 8-channel external receive coil at 3 T. Choline and citrate (Cit) signals were measured in prostate lesions and normal-appearing peripheral zone as identified on T(2)-weighted images. Metabolites were quantified relative to unsuppressed water from a separately acquired magnetic resonance spectroscopic imaging dataset using LCModel. Validation experiments were also performed in a phantom containing physiological concentrations of choline, Cit, and creatine. In vitro, fair agreement between measured and true concentrations was observed, with the greatest discrepancy being a 35% underestimation of Cit. In vivo, one dataset was rejected for failure to meet the quality criterion of linewidth <15 Hz, and in 6 of 15 subjects, insufficient normal-appearing peripheral zone tissue was identified for study. Lesions were found to have higher choline and choline/Cit, and lower Cit, than normal-appearing peripheral zone. The smaller skew of data obtained using water normalization in comparison with metabolite ratios suggests potential usefulness in longitudinal tumor monitoring and in studies of treatment effects.


In-vitro drug release testing of parenteral formulations via an agarose gel envelope to closer mimic tissue firmness.
Current in vitro drug-release testing of the sustained-release parenterals represents the in vivo situation insufficiently. In this work, a thin agarose hydrogel layer surrounding the tested dosage form was proposed to mimic the tissue. The method was applied on implantable formulations of different geometries (films, microspheres, and cylindrical implants); prepared from various polymers (several Resomer® grades or ethyl cellulose) and loaded with different model drugs: flurbiprofen, lidocaine or risperidone. The hydrogel layer did not possess any retarding effect on the released drug and acted as a physical restriction to swelling and/or plastic deformation of the tested dosage forms. This led to a different surface area available for drug-release compared with testing in release medium alone and correspondingly to significantly different release profiles of the majority of the formulations obtained between the two methods (e.g. t50% = 18 days in pure release medium vs. t50% = 26 days in gel-setup for risperidone loaded Resomer® 503 H films or t50% = 7 days vs. t50% = 19 days for risperidone loaded Resomer® 503 H microspheres). The limited space for swelling and the rigidity of the agarose gel might mimic the tight encapsulation of the dosage form in the tissue better than the conventional liquid medium.


Net primary productivity of forest stands in New Hampshire estimated from Landsat and MODIS satellite data.
A simulation model that relies on satellite observations of vegetation cover from the Landsat 7 sensor and from the Moderate Resolution Imaging Spectroradiometer (MODIS) was used to estimate net primary productivity (NPP) of forest stands at the Bartlett Experiment Forest (BEF) in the White Mountains of New Hampshire. Net primary production (NPP) predicted from the NASA-CASA model using 30-meter resolution Landsat inputs showed variations related to both vegetation cover type and elevational effects on mean air temperatures. Overall, the highest predicted NPP from the NASA-CASA model was for deciduous forest cover at low to mid-elevation locations over the landscape. Comparison of the model-predicted annual NPP to the plot-estimated values showed a significant correlation of R2 = 0.5. Stepwise addition of 30-meter resolution elevation data values explained no more than 20% of the residual variation in measured NPP patterns at BEF. Both the Landsat 7 and the 250-meter resolution MODIS derived mean annual NPP predictions for the BEF plot locations were within +/- 2.5% of the mean of plot estimates for annual NPP. Although MODIS imagery cannot capture the spatial details of NPP across the network of closely spaced plot locations as well as Landsat, the MODIS satellite data as inputs to the NASA-CASA model does accurately predict the average annual productivity of a site like the BEF.


Molecular evolutionary insights from PRLR in mammals.
Prolactin (PRL) is a pleiotropic neurohormone secreted by the mammalian pituitary gland into the blood, thus reaching many tissues and organs beyond the brain. PRL binds to its receptor, PRLR, eliciting a molecular signaling cascade. This system modulates essential mammalian behaviors and promotes notable modifications in the reproductive female tissues and organs. Here, we explore how the intracellular domain of PRLR (PRLR-ICD) modulates the expression of the PRLR gene. Despite differences in the reproductive strategies between eutherian and metatherian mammals, there is no clear distinction between PRLR-ICD functional motifs. However, we found selection signatures that showed differences between groups, with many conserved functional elements strongly maintained through purifying selection across the class Mammalia. We observed a few residues under relaxed selection, the levels of which were more pronounced in Eutheria and particularly striking in primates (Simiiformes), which could represent a pre-adaptive genetic element protected from purifying selection. Alternative, new motifs, such as YLDP (318-321) and others with residues Y283 and Y290, may already be functional. These motifs would have been co-opted in primates as part of a complex genetic repertoire related to some derived adaptive phenotypes, but these changes would have no impact on the primordial functions that characterize the mammals as a whole and that are related to the PRL-PRLR system.


Prevalence and Molecular Epidemiology of Cryptosporidium Infection in Clarias gariepinus Fish in Egypt.
This study investigated the prevalence and molecular detection of Cryptosporidium spp. in catfish (Clarias gariepinus). A total of 300 Carias gariepinus fish were collected from two freshwater sources: the Nile River (180) and drainage canals (120). The stomach and intestine epithelium of each individual fish sample were screened by modified Ziehl-Neelsen (mZN) staining technique for the detection of Cryptosporidium oocysts followed by the serological survey for detection of Cryptosporidium antibodies using Enzyme-Linked Immunosorbent Assay (ELISA) and molecular characterization using complemented DNA polymerase chain reaction (cPCR). ELISA showed higher prevalence of 69.3% than that prevalence obtained by mZN, 64% for the total examined Clarias gariepinus fish. Also, higher prevalence of Cryptosporidium infection 65.5% and 75.8% obtained by ELISA than 61.1% and 68.3% by mZN, in both fish groups from Nile River and Drainage canal, respectively. PCR analysis revealed the expected positive bands at 1056 bp. DNA sequencing and phylogenetic analysis proved that the positive-PCR Cryptosporidium isolate identified in the present study was Cryptosporidium molnari. Freshwater fishes (Clarias gariepinus) are subjected to a high infection rate with Cryptosporidium spp.; the drainage canals obtained fishes showed higher prevalence than that collected from Nile River which indicates an important public health problem and a potential risk of drainage canals in Egypt. ELISA showed higher prevalence of cryptosporidiosis than mZN, for the total examined Clarias gariepinus fish and phylogenetic analyses confirmed this protozoal organism to be a novel species of Cryptosporidium molnari.


Neutralization of Vipera and Macrovipera venoms by two experimental polyvalent antisera: a study of paraspecificity.
We conducted an extensive study of neutralization of lethality of 11 species and one subspecies of snakes of the genus Vipera, and of five species of Macrovipera, by two experimental equine antisera. One antiserum was a trivalent preparation raised against the venoms of Vipera aspis aspis, Vipera berus berus and Vipera ammodytes ammodytes; the other was a pentavalent preparation that also included venoms of Vipera (now Montivipera) xanthina and Macrovipera lebetina obtusa. We measured specific neutralization of lethality against all venoms included in the immunization schemes, and paraspecific neutralization against the venoms of Vipera ammodytes montandoni, Vipera (Montivipera) bornmuelleri, Vipera latastei, Vipera (Mo.) latifii, Vipera (Mo.) lotievi, Vipera (Daboia) palaestinae, Vipera (Mo.) raddei and Vipera seoanei, as well as against Macrovipera (D.) deserti, Macrovipera lebetina cernovi, Macrovipera lebetina turanica and Macrovipera schweitzeri. We found an important degree of paraspecific protection within each genera (omitting recent reclassification) that was quite independent of both the lethal potency of the venoms and their geographic origin. This information may be of use to clinicians charged with the treatment of Vipera or Macrovipera envenomations with non-specific antivenoms.


Oncological outcomes of laparoscopic colon resection for cancer after implementation of a full-time preceptorship.
The learning curve for laparoscopic colectomy (LC) is considered long and difficult. The presence of a preceptor may shorten the learning curve of LC and ensure adequate oncologic and short-term results. City of Hope implemented a full-time LC preceptorship between September 2004 and March 2006 with one experienced surgeon assisting other surgeons. We review our outcomes with laparoscopic colon resection for colon adenocarcinoma after implementation of this preceptorship. All cases of laparoscopic colon resection for adenocarcinoma performed from September 2004 to April 2009 were retrospectively reviewed. We compared the patients in two groups: group 1 had surgery performed during the preceptorship period from September 2004 to March 2006 (n = 39) and group 2 had procedures done between April 2006 and April 2009 (n = 74). Clinical characteristics evaluated included sex, age, body mass index (BMI), ASA level, and history of previous abdominal surgery. Postoperative variables evaluated included type of operation, conversion to open surgery, estimated blood loss (EBL), operation time, stage, number of harvested lymph nodes, time to liquid diet, postoperative stay, complications, and 30-day mortality rate. Kaplan-Meier survival curves were constructed based on disease-free survival (DFS) and overall survival (OS). One hundred thirteen patients underwent LC for adenocarcinoma during the study period. Mean age and BMI were similar between the groups. There was also no significant difference in conversion rates (10.3% vs. 13.5%, p = 0.77) or total complications (25.6% vs. 41.9%, p = 0.088) between groups 1 and 2, respectively. There was a significantly greater number of lymph nodes removed in the post-preceptor period (20.3 vs. 15.8, p = 0.007). The 3-year DFS rate was 96.5%, with a mean follow-up of 22.8 months, and the 3-year OS rate was 88.9%, with mean follow-up of 22.1 months, for the entire cohort. Implementation of a program with a full-time preceptorship can help institutions overcome the challenges of laparoscopic colectomy and achieve acceptable postoperative and oncologic outcomes.


Hyperthermia depletes adenosine triphosphate and decreases glutamate uptake in rat hippocampal slices.
The central nervous system is especially vulnerable to hyperthermia-induced dysfunction, yet the mechanism for this susceptibility is poorly understood. High levels of adenosine triphosphate are necessary to maintain normal re-uptake of glutamate and aspartate, the major excitatory amino acids, by excitatory amino acid co-transporters. We hypothesized that excitotoxic neurotransmitters accumulate extracellularly when hyperthermia depletes adenosine triphosphate, leading to decreased uptake or release of excitatory amino acids by these co-transporters. Incubation of hippocampal slices at 42 degrees C, a temperature that results in coma in vivo, reduced adenosine triphosphate to 70% of control values and decreased uptake of the transportable excitatory amino acid analogue, D,L threo-beta-hydroxyaspartate, to 50% of control values. The degree of adenosine triphosphate depletion induced by hyperthermia was highly correlated with decreases in excitatory amino acid uptake. Severe adenosine triphosphate depletion (< or = 20% of control) induced by hyperthermia in combination with metabolic insults was highly correlated with the release of endogenous glutamate and aspartate. Preloading slices with excitatory amino acid analogues potentiated hyperthermia-induced alterations of excitatory amino acid transport, strongly suggesting that the hyperthermia-induced changes were largely due to altered excitatory amino acid co-transporter activity. Immunocytochemical studies suggested glutamate-like immunoreactivity was lost from axonal terminals during hyperthermia in a similar manner to losses induced by metabolic toxins. Hyperthermia due to infectious diseases or heat stroke my induce disorientation and coma. These dysfunctions may be due, in part, to altered excitatory amino acid transport induced by adenosine triphosphate depletion.


Extraction, profiling and bioactivity analysis of volatile glucosinolates present in oil extract of Brassica juncea var. raya.
Cruciferous vegetables are rich source of glucosinolates (GSLs), which in presence of myrosinase enzyme cause hydrolytic cleavage and result in different hydrolytic products like isothiocyanates, thiocyanates, nitriles and epinitriles. The GSLs hydrolytic products are volatile compounds, which are known to exhibit bioactivities like antioxidant, fungicidal, bioherbicidal and anticancer. Among the Brassicaceae family, Brassica juncea is very well known for high content of GSLs. In the present study, the isolation of volatile oil of B. juncea var. raya was done by hydrodistillation method using clevenger apparatus and further there extraction was done by solvents ethyl acetate and dichloromethane. The volatile compounds present in the extract were analysed by gas chromatography/gas chromatography-mass spectrometry (GC/GC-MS). Fatty acid esters, sulphur and/or nitrogen compounds, carbonyl compounds and some other volatile compounds were also identified. Besides the analytical studies, the extracts were analysed for their bioactivities including radical scavenging activity by using DNA nicking assay and cytotoxic effect using different human cancer cell lines viz. breast (MCF-7 and MDA-MB-231), prostate (PC-3), lung (A-549), cervix (HeLa) and colon (HCT116) by MTT assay. The oil extracts were efficiently able to reduce the increase of cancer cells in a dose-dependent manner. Among all cell lines, the most effective anticancer activity was observed in case of breast (MCF-7) cancer cell line. So, MCF-7 cells were used for further mechanistic studies for analysing the mechanism of anticancer activity. Confocal microscopy was done for analysing morphological changes in the cells and the images confirmed the features typical of apoptosis. For evaluating the mode of cell death, spectrofluorometric determination of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) was done. The volatile oil extract treated MCF-7 cells had a significant increase in number of ROS, also there was a rise in percentage of cells with increased disruption of MMP. So, the present study marks necessary indication that B. juncea (raya) oil extracts significantly induces apoptosis in all the above mentioned cancer cells lines through a ROS-mediated mitochondrial pathway and thus play a remarkable role in death of cancer cells.


Ubiquitin receptors and ERAD: a network of pathways to the proteasome.
The elimination of misfolded proteins, known as protein quality control, is an essential cellular process. Removal of misfolded proteins from the secretory pathway depends on their recognition in the endoplasmic reticulum (ER) followed by their retrograde transport into the cytosol for degradation. The AAA-ATPase Cdc48/p97 facilitates the translocation of misfolded ER-proteins into the cytosol. Cdc48/p97 can dock onto the ER-membrane via direct interaction with ER-membrane proteins and/or indirectly via its substrate-recruiting cofactors, which interact with the ubiquitylated substrates at the membrane. This tight interaction in conjunction with the conformational changes induced upon ATP hydrolysis within Cdc48/p97 is thought to provide the driving force for the translocation reaction. Subsequently, a series of protein-protein interactions between the Cdc48/p97 complex, its cofactors, and the ubiquitylated substrates is instrumental for the proper delivery of the ER substrates to the proteasome. These protein-protein interactions are governed mainly by ubiquitin-fold and ubiquitin-binding domains.


Effect of living alone on patient outcomes after hospitalization for acute myocardial infarction.
Considerable attention has been devoted to the effect of social support on patient outcomes after acute myocardial infarction (AMI). However, little is known about the relation between patient living arrangements and outcomes. Thus, we used data from PREMIER, a registry of patients hospitalized with AMI at 19 United States centers from 2003 through 2004, to assess the association of living alone with outcomes after AMI. Outcome measurements included 4-year mortality, 1-year readmission, and 1-year health status using the Seattle Angina Questionnaire (SAQ) and the Short Form-12 Physical Health Component scales. Patients who lived alone had higher crude 4-year mortality (21.8% vs 14.5%, p <0.001) but comparable rates of 1-year readmission (41.6% vs 38.3%, p = 0.79). Living alone was associated with lower unadjusted quality of life (mean SAQ -2.40, 95% confidence interval [CI] -4.44 to -0.35, p = 0.02) but had no impact on Short Form-12 Physical Health Component (-0.45, 95% CI -1.65 to 0.76, p = 0.47) compared to patients who did not live alone. After multivariable adjustment, patients who lived alone had a comparable risk of mortality (hazard ratio 1.35, 95% CI 0.94 to 1.93) and readmission (hazard ratio 0.99, 95% CI 0.76 to 1.28) as patients who lived with others. Mean quality-of-life scores remained lower in patients who lived alone (SAQ -2.91, 95% CI -5.56 to -0.26, p = 0.03). In conclusion, living alone may be associated with poorer angina-related quality of life 1 year after MI but is not associated with mortality, readmission, or other health status measurements after adjusting for other patient and treatment characteristics.


Study on the regulatory mechanism of the earthworm microbial community in vitro and in vivo under cadmium stress.
In this paper, cadmium (Cd) stress tests were performed on Eisenia fetida in sterile artificial soil, and its regulatory mechanism between microbial communities in vivo and in vitro after Cd stress was explored. In the test, 0, 50, 100, 125, 250 and 500 mg kg-1 Cd stress concentrations were implemented. After long-term and short-term stress, the microbes in the earthworms and the soil were cultured with ECO plates. The data statistics of carbon source utilization intensity were carried out using the method developed by our team. CCA was scientifically integrated into TOPSIS to establish a new data analysis model to find the regulatory nodes after stress (Ning et al., 2020). Macro gene sequencing technology revealed that the species with the highest absolute abundance in the microbial communities in vivo and in vitro were all unnamed new species. It was confirmed that the HBA gene, NEUROD1 gene and ABCA3 gene were the regulatory genes of the microbial community in the earthworms under Cd stress, while the TC.FEV.OM gene and cheBR gene were the main regulatory genes of the microbial community in the soil. These results provide a scientific and theoretical reference and model basis for the bioremediation of Cd-contaminated soil and the detoxification mechanism of earthworms.


Peptidomic analysis of skin secretions from the bullfrog Lithobates catesbeianus (Ranidae) identifies multiple peptides with potent insulin-releasing activity.
Using a combination of reversed-phase HPLC and electrospray mass spectrometry, peptidomic analysis of norepinephrine-stimulated skin secretions of the American bullfrog Lithobates catesbeianus Shaw, 1802 led to the identification and characterization of five newly described peptides (ranatuerin-1CBb, ranatuerin-2CBc, and -CBd, palustrin-2CBa, and temporin-CBf) together with seven peptides previously isolated on the basis of their antimicrobial activity (ranatuerin-1CBa, ranatuerin-2CBa, brevinin-1CBa, and -1CBb, temporin-CBa, -CBb, and -CBd). The abilities of the most abundant of the purified peptides to stimulate the release of insulin from the rat BRIN-BD11 clonal β cell line were evaluated. Ranatuerin-2CBd (GFLDIIKNLGKTFAGHMLDKIRCTIGTCPPSP) was the most potent peptide producing a significant stimulation of insulin release (119% of basal rate, P<0.01) from BRIN-BD11 cells at a concentration of 30nM, with a maximum response (236% of basal rate, P<0.001) at a concentration of 3μM. Ranatuerin-2CBd did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3μM, indicating that the integrity of the plasma membrane had been preserved. Brevinin-1CBb (FLPFIARLAAKVFPSIICSVTKKC) produced the maximum stimulation of insulin release (285% of basal rate, P<0.001 at 3μM) but the peptide was cytotoxic at this concentration.


Erratum: Look to the stars-Is there anything that public health and rehabilitation can learn from elite sports?
[This corrects the article DOI: 10.3389/fspor.2022.1072154.].


High-flow oxygen via tracheostomy facilitates weaning from prolonged mechanical ventilation in patients with restrictive pulmonary dysfunction: two case reports.
Weaning from prolonged mechanical ventilation is extremely difficult in tracheostomized patients with restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy supplies heated and humidified oxygen gas at > 10 L/minute. However, little has been reported on the use of high-flow oxygen via tracheostomy during weaning from ventilators in patients with restrictive pulmonary dysfunction. We report successful weaning from ventilators in patients with restrictive pulmonary dysfunction using high-flow oxygen via tracheostomy. The first patient is a 78-year-old Japanese man with severe pneumococcal pneumonia who was mechanically ventilated for more than 1 month after esophagectomy for esophageal cancer. After he underwent tracheostomy because of prolonged mechanical ventilation, restrictive pulmonary dysfunction appeared: tidal volume 230-240 mL and static compliance 14-15 mL/cmH2O with 10 cmH2O pressure support ventilation. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 16 days (flow at 40 L/minute and fraction of inspired oxygen of 0.25). The second patient is a 69-year-old Japanese man who developed aspiration pneumonia after esophagectomy and received prolonged mechanical ventilation via tracheostomy. He developed restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy (flow at 40 L/minute with fraction of inspired oxygen of 0.25) was administered with measurement of the airway pressure and at the entrance of the tracheostomy tube. The measured values were as follows: 0.21-0.3 cmH2O, 0.21-0.56 cmH2O, 0.54-0.91 cmH2O, 0.76-2.01 cmH2O, 1.17-2.01 cmH2O, and 1.76-2.01 cmH2O at 10 L/minute, 20 L/minute, 30 L/minute, 40 L/minute, 50 L/minute, and 60 L/minute, respectively. The airway pressures were continuously positive and did not become negative even during inspiration, suggesting that high-flow oxygen via tracheostomy reduces inspiratory effort. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 12 days. High-flow oxygen via tracheostomy may reduce the inspiratory effort and enhance tidal volume by delivering high-flow oxygen and facilitate weaning from prolonged mechanical ventilation in patients with restrictive pulmonary dysfunction.


The effect of posterior rectopexy on fecal continence. A prospective study.
Twenty-three patients with rectal prolapse or intussusception were studied to specifically focus on the effect of posterior rectopexy on fecal continence, anal pressure, and rectal capacity. Before operation, five patients were fully continent (A), 10 were continent for solid stools (B) and eight patients were fully incontinent (C). Group A remained fully continent; continence was regained nine times in group B and in group C, three patients regained full continence, two became continent for solid stools, three patients remained incontinent. Other symptoms such as constipation, false urgency, and a feeling of incomplete evacuation were not beneficially influenced by rectopexy. The patients' continence status was correlated to anorectal manometry and rectal capacity measurement. In group B, incremental pressure (P = squeeze - basal P) increased significantly (P less than 0.02) as well as incremental volume (V = maximum tolerated volume - volume of first sensation) (P less than 0.05). We conclude that, by an increase of incremental anal pressure and incremental rectal volume, posterior rectopexy offers an 83 percent chance of regaining full continence, or a major improvement, and a 17 percent chance of stabilization of fecal incontinence.


Explusion of SALIBI-clamp from the internal carotied artery in the neck by infection.
A left infraclinoid carotid aneurysm (3 x 2-5 x 2 cm) in a 60-year old woman presented with total ophthalmoplegia and trigeminal symptoms. A staged internal carotied occlusion in the neck was performed using a SALIBI-clamp. A chronic infectious fistula developed (Klebsiella aerogenes). When superficial debridement failed, operative removal of the SALIBI-clamp was planned seven months after its insertion. The clamp was found subcutaneously without any relation to the internal carotid artery and was easily removed. Subsequent catheter angiography proved the left internal carotied to be completely occluded in the neck. No cross filling of the aneurysm could be demonstrated from the right carotied nor the vertebro-basilar arteries. The neurological deficit remained unchanged. The wound closed promptly without further signs of infection.


Indolo[3,2,1-jk]carbazole Embedded Multiple-Resonance Fluorophors for Narrowband Deep-blue Electroluminescence with EQE≈34.7 % and CIEy ≈0.085.
Multiple-resonance (MR) organic emitters bearing small full-width at half-maximum (FWHMs) are of general interest in organic light-emitting diodes. Indolo[3,2,1-jk]carbazole (ICz) embedded MR-fluorophors have demonstrated extremely small FWHMs, yet in the violet region with low electroluminescence efficiency. Herein, a strategic implementation of ICz subunits into MR fluorophors is proposed by taking advantage of the synergetic effect of para-positioned nitrogen atoms to enhance electronic coupling to decrease emitting energy gap. Deep blue emitters peaking at 441 and 447 nm with FWHMs of only 18 and 21 nm are thereof obtained, respectively, accompanied by ≈90 % photo-luminance quantum yields. With the assistance of a thermally activated delayed fluorescence sensitizer to recycle excitons, the corresponding narrowband electroluminescent devices show unprecedent high maximum external quantum efficiencies of 32.0 % and 34.7 % with CIEy of 0.10 and 0.085, respectively.