Effects of atrazine and chlorpyrifos on the production of nitric oxide and expression of inducible nitric oxide synthase in the brain of common carp (Cyprinus carpio L.).
The study aimed to investigate the effects of atrazine (ATR), chlorpyrifos (CPF), and the mixture of them on nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in the brain of common carp. The triazine herbicide ATR and the organophosphorus insecticide CPF are frequently and extensively applied in agriculture all over the world. 220 Carps were averagely divided into eleven groups according to the different treatments and concentration, including the exposure and recovery experiments. In the present study, we investigated production of NO, iNOS activity and iNOS mRNA and protein expression in the brain of the common carp after a 40d exposure to ATR, CPF, alone or in combination, and a 40d recovery treatment. The results showed that the activity of iNOS and production of NO were significantly higher in all groups of fish exposed to high doses ATR, CPF and their mixture compared to control fish. After a 40d recovery treatment, iNOS activity and production of NO were lower than in the corresponding exposure groups in all the recovery groups. The mRNA and protein levels of iNOS were significantly higher in the high-dose group of ATR and CPF compared to control group, but were significantly lower in the group of the mixture of ATR and CPF compared to control group. Results indicated that NO and iNOS were involved in oxidative stress and brain tissue damage induced by ATR, CPF, and their mixture. Thus, the information presented in this study is helpful to understand the mechanism of ATR-, CPF- and ATR/CPF-mixture-induced neurotoxicity in fish.


Benign villous polyp with prostatic type epithelium of the penile urethra.
We report a case of a benign polyp of the penile urethra composed of prostatic type epithelial tissue. The etiology, pathology, diagnosis and treatment of these uncommon lesions are discussed.


Routine histological analysis of resected lung tissue in primary spontaneous pneumothorax -- is it justified?
Surgical management of spontaneous primary pneumothorax consists of pleurectomy together with resection of blebs or bullae. We analysed the utility of routine histological examination of these resected specimens. A consecutive series of 64 resected specimens were reviewed, of which 43 (67%) showed the presence of bullae or blebs. Of the remainder, 20 (31%) specimens showed no evidence of bullae or blebs and 1 specimen showed the presence of pneumatocoeles. Examination of the lung parenchyma revealed inflammation in 34 (53%) cases. In all 64 cases, the histological results did not result in a change in medical therapy. Although resected lung specimens from patients with primary spontaneous pneumothorax show diversity in their histological characteristics, we would question the utility of routine pathological analysis of resected lung specimens in primary spontaneous pneumothorax.


Sigma- and pi- electron structure of aza-azoles.
The reasons behind changes of aromaticity in 10 unsubstituted aza-azoles were analysed by employing the natural bond orbital (NBO) approach at the MP2/6-311+G(d,p) level of theory. Sum of occupations of p(z) orbitals at atoms in the ring correlates well with the magnetism based aromaticity index NICS as well as with the number of nitrogen atoms in the ring. Changes of NICS depend strongly in a linear way on the number of NN bonds. Classification of azoles based on the number of pyridine-type nitrogen atoms vicinal to NH is supported by plotting the relative occupation of π orbitals (π(occ)) against the relative occupation of σ orbitals (σ(occ)) for all individual atoms in rings.


Diversity of human parechoviruses in Bulgaria, 2011: Detection of rare genotypes 8 and 10.
Human parechovirus (HPeV) infections are commonly asymptomatic but are also found in association with symptoms of the gastrointestinal and respiratory tract, or central nervous system. In order to study their distribution and genetic diversity in Bulgaria, specimens from 229 children aged <5years old hospitalized due to neurological manifestations (n=104) and acute gastroenteritis (n=125) were analyzed. Stool samples were tested using reverse transcription followed by real-time polymerase chain reaction toward the 5'UTR region, and the HPeVs detected were identified by PCR directed to VP1 followed by sequencing. HPeV infection rates of 1.9% and 7.2% were found in children presented with neurological symptoms or with acute diarrhea, respectively. Four different HPeV genotypes, HPeV-3 (n=2), HPeV-5 (n=2), HPeV-8 (n=1) and HPeV-10 (n=1) were identified. All but two HPeVs were detected in acute diarrheal cases, while a single HPeV-3 strain and an HPeV-8 strain were detected in association with facial palsy and encephalitis, respectively. This is the first report of HPeV-8 and HPeV-10 in Europe.


Biological embedding vs. embodiment of social experiences: How these two concepts form distinct thought styles around the social production of health inequalities.
This article compares research on biological embedding and the embodiment of social experiences, two concepts proposed in the 1990s to introduce a new perspective on the social production of health inequalities. We draw on Ludwig Fleck's concept of 'thought style' (1935/2008) to question the possible emergence of a common research program around the processes by which the social becomes biological. We compiled a corpus of 322 articles referring to either biological embedding or to the embodiment of social experiences, identified in the Web of Science core collection and published from 1990 to 2021. We analyzed the articles' use of these concepts using scientometric indicators and qualitative content analysis. Initial differences between the research agendas associated with biological embedding and embodiment are strengthened as both concepts circulate around scientific communities studying the social production of health inequalities. Thought styles formed around embedding and embodiment differ significantly in terms of shared references, sets of methods and research questions, and policy recommendations. Research on biological embedding forms a thought style shared by researchers in the biomedical and public health sciences. Conversely, the concept of embodiment of social experiences connects perspectives from biomedical, public health, human and social sciences, and gathers three thought styles, one identical to that of biological embedding and two formed in social epidemiology and in medical anthropology. Acknowledging the differences between the concepts and divergences in their evolution provides an opportunity for identification of topics where thought styles are either complementary or in tension.


Collateral benefits and hidden hazards of soil arsenic during abatement assessment of residential lead hazards.
Abatement of soil-lead hazards may also reduce human exposure to other soil toxins, thereby achieving significant collateral benefits that are not accounted for today. This proposition was tested with the specific case of soil-arsenic, where 1726 residential soil samples were collected and analyzed for lead and arsenic. The study found that these two toxins coexisted in most samples, but their concentrations were weakly correlated, reflecting the differing sources for each toxin. Collateral benefits of 9% would be achieved during abatement of the lead-contaminated soils having elevated arsenic concentrations. However, a hidden hazard of 16% was observed by overlooking elevated arsenic concentrations in soils having lead concentrations not requiring abatement. This study recommends that soil samples collected under HUD programs should be collected from areas of lead and arsenic deposition and tested for arsenic as well as lead, and that soil abatement decisions consider soil-arsenic as well as soil-lead guidelines.


The Yin and Yang of R-loop biology.
RNA performs diverse functions in cells, directing translation, modulating transcription and catalyzing enzymatic reactions. Remarkably RNA can also anneal to its genomic template co- or post-transcriptionally to generate an RNA-DNA hybrid and a displaced single-stranded DNA. These unusual nucleic acid structures are called R-loops. Studies in the last decades concentrated on the detrimental effects of R-loop formation, particularly on genome stability. In fact, R-loops are thought to play a role in several human diseases like cancer and neurodegenerative syndromes. But recent data has revealed that R-loops can also have a positive impact on cell processes, like regulating gene expression, chromosome structure and DNA repair. Here we summarize our current understanding of the formation and dissolution of R-loops, and discuss their negative and positive impact on genome structure and function.


Efficient induction of ginsenoside biosynthesis and alteration of ginsenoside heterogeneity in cell cultures of Panax notoginseng by using chemically synthesized 2-hydroxyethyl jasmonate.
Chemically synthesized 2-hydroxyethyl jasmonate (HEJA) was for the first time employed to induce the ginsenoside biosynthesis and to manipulate the product heterogeneity in plant cell cultures. The dose response and timing of HEJA elicitation were investigated in cell suspension cultures of Panax notoginseng. The optimal concentration and timing of HEJA addition for both cell growth and ginsenoside accumulation was identified to be 200 microM added on day 4. It was interestingly found that HEJA could stimulate ginsenosides biosynthesis and change their heterogeneity more efficiently than methyl jasmonate (MJA), i.e., the total ginsenoside content and the Rb/Rg ratio increased about 60 and 30% with HEJA elicitation than that by MJA, respectively. The activity of Rb1 biosynthetic enzyme, i.e., UDPG-ginsenoside Rd glucosyltransferase (UGRdGT), was also higher in the former case. A maximal production titer of ginsenoside Rg1, Re, Rb1, and Rd was 47.4+/-4.8, 52.3+/-4.4, 190+/-18, and 12.1+/-2.5 mg/l with HEJA elicitation, which was about 1.3-, 1.3-, 1.7-, and 2.1-fold than that using MJA, respectively. Early signal events in plant defense response, including oxidative burst and jasmonic acid (JA) biosynthesis, were also examined. Levels of H2O2 and NO in medium and L-phenylalanine ammonia lyase activity in cells were not affected by addition of MJA and HEJA. On the other hand, the JA content in cells was increased with external jasmonates elicitation, and it was inhibited with the addition of JA biosynthesis inhibitors. The results suggest that oxidative burst might not be involved in the jasmonates-elicited signal transduction pathway, and MJA and HEJA may induce the ginsenoside biosynthesis via induction of endogenous JA biosynthesis and key enzymes (such as UGRdGT) in the ginsenoside biosynthetic pathway of P. notoginseng cells. The information is useful for hyperproduction of plant-specific heterogeneous products.


Bulevirtide: First Approval.
Bulevirtide (Hepcludex®), a first-in-class entry inhibitor, is being developed by MYR GmbH for the treatment of chronic hepatitis delta virus (HDV) and chronic hepatitis B virus (HBV) infections. Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease. This article summarizes the milestones in the development of bulevirtide leading to this first approval for chronic HDV.


Emergency treatment with recombinant tissue plasminogen activator of pulmonary embolism in a pregnant woman with antithrombin III deficiency.
Thromboembolic complications during pregnancy are frequent in patients with congenital antithrombin III deficiency. We report on a 29-year-old patient with congenital antithrombin III deficiency and severe pulmonary embolism treated with recombinant tissue plasminogen activator. The diagnosis of antithrombin deficiency is retrospective. This case indicates that the risk of thrombolytic therapy in this clinical setting might have been overemphasized.


Implementing Head and Neck Contouring Peer Review without Pathway Delay: The On-demand Approach.
Peer review of contour volume is a priority in the radiotherapy treatment quality assurance process for head and neck cancer. It is essential that incorporation of peer review activity does not introduce additional delays. An on-demand peer review process was piloted to assess the feasibility and efficiency of this approach, as compared with a historic scheduled weekly approach. Between November 2016 and April 2017 four head and neck clinicians in one centre took part in an on-demand peer review process. Cases were of radical or adjuvant intent of any histology and submitted on a voluntary basis. The outcome of contour peer review would be one of unchanged (UC), unchanged with variation or discretion noted (UV), minor change (M) or significant change (S). The time difference between the completion of the on-demand peer review was compared with the time difference to a hypothetical next Monday or Tuesday weekly peer review meeting. The time taken to review each case was also documented in the latter period of the pilot project. In total, 62 cases underwent peer review. Peer review on-demand provided dosimetrists with an average of an extra two working days available per case to meet treatment start dates. The proportion of cases with outcomes UC, UV, M and S were 45%, 16%, 26% and 13%, respectively. The mean peer review time spent per case was 17 min (12 cases). The main reason for S was discrepancy in imaging interpretation (4/8 cases). A lower proportion of oropharyngeal cases were submitted and had S outcomes. A higher proportion of complex cases, e.g. sinonasal/nasopharynx location or previous downstaging chemotherapy had S outcomes. The distribution of S outcomes appears to be similar regardless of clinician experience. The level of peer review activity among individuals differed by workload and job timetable. On-demand peer review of the head and neck contour volume is feasible, reduces delay to the start of dosimetry planning and bypasses the logistical barriers of weekly meetings. An audit of participation will be required to ensure successful implementation.


Pre-treatment but not co-treatment with vitexin alleviates hyperthermia induced oxidative stress and inflammation in buffalo mammary epithelial cells.
This study investigated if in vitro supplementation of vitexin could mitigate the adverse effects of hyperthermia on buffalo mammary epithelial cells (BuMECs). Immortalized BuMECs were divided into seven groups (n = 3): (1) a negative control group at 37 °C; (2) BuMECs exposed to heat stress as a positive control at 42 °C for 1 h; (3-7) heat stressed BuMECs pre-treated or co-treated with different concentrations of vitexin (5 μM, 10 μM, 20 μM, 50 μM, and 100 μM), respectively. Hyperthermia was induced by exposing the cells to 42 ºC for 1 h. For the pre-treatment experiment, BuMECs were treated with vitexin for 2 h before hyperthermia exposure. For co-treatment, vitexin was added simultaneously with hyperthermia for 1 h. Subsequently, the cells were allowed to recover for 12 h at 37 °C. Results showed that pre-treatment with vitexin was more effective than co-treatment in protecting BuMECs from hyperthermia in a dose-dependent manner, with higher concentrations (50 μM and 100 μM) being the most effective. Pre-treatment with vitexin maintained cellular viability and prevented inflammation by inducing the expression of the anti-apoptotic gene (BCL-2) and reducing the expression of the pro-apoptotic gene (Bax) and pro-inflammatory mediators (IL-1β, IL-6) in heat-stressed BuMECs. Pre-treatment with vitexin reduced oxidative stress and induced thermotolerance by increasing the expression of antioxidants mediators such as SOD, GPx and CAT at mRNA and protein levels, and modulating the expression of heat shock proteins. The findings suggest that vitexin has the potential as a therapeutic agent to protect the mammary gland from the negative impact of hyperthermia in dairy cows.


Healthcare Professionals' Knowledge of and Attitudes Towards the Use of Time in Range in Diabetes Management: Online Survey Across Seven Countries.
Time in range (TIR) is a metric of glycaemic target management derived from continuous glucose monitoring (CGM) data. This study aimed to understand knowledge of and attitudes towards use of TIR among healthcare professionals (HCPs), and gain insights into benefits and barriers to its use in clinical practice. An online survey was disseminated across seven countries. Participants were sampled from online HCP panels and were aware of TIR (defined as amount of time in, below, and above target range). Participants were HCPs classified as specialists (SP), generalists (GP), or allied HCPs (AP; diabetes nurse specialists, diabetes educators, general nurses, nurse practitioners/physician assistants). Respondents included 741 SP, 671 GP and 307 AP. Most HCPs (approximately 90%) agreed TIR is likely/somewhat likely to become the standard of diabetes management. Perceived benefits of TIR included helping to optimise medication regimen (SP, 71%; GP, 73%; AP, 74%), giving HCPs the knowledge and insights to make informed clinical decisions (SP, 66%; GP, 61%; AP, 72%), and empowering people with diabetes with information to successfully manage their diabetes (SP, 69%; GP, 77%; AP, 78%). Barriers to wider adoption included limited CGM access (SP, 65%; GP, 74%; AP, 69%) and lack of HCP training/education (SP, 45%; GP, 59%; AP, 51%). Most participants considered integration of TIR into clinical guidelines, recognition of TIR by regulators as a primary clinical endpoint, and recognition of TIR by payers as a parameter for diabetes treatment evaluation as key factors for increased use. Overall, HCPs agreed on the benefits of using TIR for diabetes management. Besides raising awareness among HCPs and people with diabetes, more training and healthcare system updates are needed to facilitate increased TIR use. In addition, integration into clinical guidelines and recognition by regulators and payers are needed.


Cognitive Enhancement Through Mathematical Problem-Solving.
Nowadays, modern lifestyle along with the ever-growing technological and scientific advancement, especially in developed countries, has led to a significant increase of the middle age and elderly population. As a consequence, a substantial rise in neurodegenerative diseases has been reported, such as mild cognitive impairment, Alzheimer's disease, and other types of dementia. The aim of this paper is to study the impact of mathematical problem-solving on cognitive enhancement of adults. Moreover, the possible applicability of mathematical problem-solving as part of a treatment in cases of adults suffering from different levels of cognitive decline due to neurodegenerative diseases has been taken into consideration. For the needs of this study, a qualitative research was conducted in a sample of 16 participants, in order to confirm the effect of the mathematical problem-solving process on their cognition and its reinforcement, as stated by the participants. The results of this research, as interpreted, indicate a positive effect of mathematical problem-solving on adult cognition and on cognitive processes in general. Nonetheless, there are certain limitations to this research, deriving from its nature, while others derive from the measures enforced during the SARS-CoV-2 outbreak. Therefore, this chapter suggests that a more thorough quantitative research should be conducted in order to specifically measure the magnitude, as well as the time span of the impact of mathematical problem-solving on adult cognitive enhancement. Moreover, it is proposed that future studies should concentrate on the usefulness of mathematical problem-solving as a component in both invasive and noninvasive cognitive treatments used to cure or alleviate the aforementioned cognitive impairments.


Conservative management of an unusual bilioduodenal fistula post laparoscopic Duodeno-Ileal Switch (SADI-S) case report.
Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is an advanced operation for morbid obesity. To our knowledge, no internal Biliodigestive Fistula has yet been reported as specific complication in the field of metabolic and bariatric Biliopancreatic diversion. In this case report, we detail the case of a 57-year-old man who underwent a Single Anastomosis Duodeno-Ileal Switch (SADI-S) bariatric procedure for morbid obesity. Upon admission 3 weeks after the SADI-S procedure acute sepsis caused by a delayed choledoco-duodenal Fistula was diagnosed. A conservative management of this rare complication was successful. We highlight the differential diagnosis and optional treatment in such a rare complication, and how we succeeded in its conservative management, without any need for endoscopic nor surgical intervention. A review of the literature on different types of Internal Biliodigestive Fistulae and their appropriate management are reported and briefly discussed. The aim of this case report is to highlight the existence of such a rare complication, and its successful multidisciplinary conservative medical management.


A revised subgeneric position for Polypedilum (Probolum) simantokeleum, with description of a new Uresipedilum species in Japan (Diptera: Chironomidae).
Two Japanese Polypedilum species including a new species are redescribed and described based on the males. Polypedilum (Probolum) simantokeleum, Sasa, Suzuki et Sakai, 1998, is transferred to the subgenus Uresipedilum. Polypedilum (Uresipedilum) dissimilum sp. nov. is easily distinguished from other members of Uresipedilum by having a T-shaped tergal band. Definition of the subgenus Probolum is briefly discussed: we suggest Probolum should be defined as the species with the superior volsella bearing inner lobe pending adequate larval information.


Comparison of the outcome of implantation of hydrophobic acrylic versus silicone intraocular lenses in pediatric cataract: prospective randomized study.
To compare the postoperative performance of hydrophobic acrylic and silicone square-edge intraocular lenses in pediatric cataract. Prospective randomized study. Forty-one eyes of 41 children (age 1 month to 8 years) with congenital or developmental cataract. Children were randomly divided into 2 groups. All participants underwent phacoaspiration, primary posterior capsulotomy, and anterior vitrectomy. Group A (n = 21) eyes were implanted with acrylic hydrophobic AcrySof SA60AT intraocular lenses (IOLs), and those of Group B (n = 20) were implanted with silicone Tecnis Z9000 IOLs. The children were evaluated for anterior chamber reaction, IOL position, posterior capsular opacification PCO), intraocular pressure, best-corrected visual acuity (BCVA), corneal status, and refractive errors. Postoperatively, 2 eyes in each group had significant anterior chamber reaction with fibrin membrane formation. IOLs were in the capsular bag in all but 1 eye in both groups. Seven eyes in the acrylic group and 6 eyes in the silicone group achieved visual acuity of 20/40 or better. None of the eyes showed glaucoma. BCVA at 1 year was similar in both groups. In the acrylic hydrophobic group, 14 eyes needed hypermetropic correction and 7 eyes were myopic, and in the silicone group 10 eyes had myopia and 10 eyes had hypermetropia at 1 year postoperatively. PCO at 1 year follow-up was more common in eyes implanted with acrylic hydrophobic IOLs (5 eyes) than silicone IOLs (2 eyes). Both square-edge hydrophobic acrylic and silicone IOLs were found to be compatible and safe for use in pediatric cataract surgery with similar visual axis clarity and postoperative outcome.


Junctional transfer in cultured vascular endothelium: I. Electrical coupling.
Vascular endothelial cultures are composed of flat, polygonal monolayer cells which retain many of the growth, metabolic and physiological characteristics of the intimal endothelium. However, intercellular gap and tight junctions, which are thought to perform important roles in normal intimal physiology, are reduced in complexity and extent in culture. We have used electrophysiological techniques to test confluent (3- to 5-day) primary cultures of calf aortic (BAEC) and umbilical cord vein (BVEC) endothelium for junctional transfer of small ions. Both cell types are extensively electrically coupled. The passive electrical properties of the cultured cells were calculated from the decrease in induced membrane potential deflections with distance from an intracellular, hyperpolarizing electrode. Data analyses were based on a thin-sheet model for current flow (Bessel function). The generalized space constants (lambda) were 208.6 microns (BAEC) and 288.9 microns (BVEC). The nonjunctional (6.14 and 8.72 X 10(8) omega) and junctional (3.67 and 3.60 X 10(6) omega) resistances were similar for the BAEC and BVEC, respectively. We detected no statistically significant differences in the resistance estimates for the two cell types. In vivo ultrastructural studies have suggested that aortic endothelium has more extensive gap junctions than venous endothelium. We have found that these ultrastructural differences are reduced in culture. The lack of any significant difference in electrical coupling capability suggests that cultured BAEC and BVEC have functionally similar junctional characteristics.


Endoluminal repair of axillary artery and vein rupture after reduction of shoulder dislocation. A case report.
A case of endoluminal repair of vein and artery axillary rupture after reduction of shoulder dislocation in an 83-year-old woman is reported. The lesions were repaired successfully with two cover stents (JOSTENT and Passager). Endovascular treatment of such vascular injuries seems to be feasible and safe, though further investigation is warranted.


Neural processing of odor-associated words: an fMRI study in patients with acquired olfactory loss.
Perception of olfactory information is mediated by both bottom-up (from molecules to perception) and top-down (e.g. cross-modal associative learning) processes. Acquired olfactory loss is a frequent disorder which is typically due to alterations in the bottom-up pathway. However, it is unclear how the top-down modulation of olfactory processing is affected by olfactory impairment. Our study aimed to investigate the top-down olfactory processing in patients with acquired olfactory loss and participants with normal olfaction. Using functional MRI, brain responses from 14 patients and 16 healthy controls were assessed during a task of expectation and reading of words with strong olfactory associations (OW) (e.g. "Rose") and control words with little to no olfactory associations (CW) (e.g. "Door"). The expectation but not reading of the OW was associated with stronger neural activation in the angular gyrus and the inferior frontal gyrus extending to insula in the group of patients. During OW reading, the brain activation in the left OFC and right putamen was negatively correlated with odor identification score in patient and control groups, respectively. In addition, the duration of olfactory loss among patients was positively associated with activation in the left putamen during OW expectation. Taken together, these findings suggest an enhanced top-down olfactory modulation in patients with olfactory loss.


The use of 96-well polystyrene plates for DNA hybridization-based assays: an evaluation of different approaches to oligonucleotide immobilization.
A reliable, simple, and cost-effective method for the immobilization of relatively short (12-30 mer) oligonucleotide probes to 96-well polystyrene plates was required in our laboratory for use in DNA hybridization-based assays. We compared three different approaches to achieve this immobilization. Two of them are modifications of previously published procedures, requiring the use of modified oligonucleotides and/or modified plates. These were compared to a method developed in our laboratory, whereby passive immobilization occurs by incubation in the presence of salt or a cationic detergent. While all methods resulted in the productive binding of the DNA probes and could therefore be used for hybridization, only the passive immobilization approach met our strict performance criteria and was implemented for use in our DNA genotyping laboratory. It was found that the immobilization in the presence of cationic detergents takes place via a unique mechanism.


Calcium Oscillatory Patterns and Oocyte Activation During Fertilization: a Possible Mechanism for Total Fertilization Failure (TFF) in Human In Vitro Fertilization?
This paper reviews the effects of calcium oscillatory patterns in oocytes and early embryo development. Total fertilization failure (TFF) is the failure of fertilization in all oocytes in a human IVF cycle, even after treatment with intracytoplasmic sperm injection (ICSI). It is not well understood and currently attributed to oocyte activation deficiency. Calcium signaling is important in oocyte activation events. Calcium oscillations, in particular, have been reported in animal and human oocytes after fertilization. Abnormal calcium oscillations after fertilization may be the principal mechanism for TFF. While studies also establish strong associations between abnormal calcium oscillatory patterns and suboptimal developmental outcomes, critical basic parameters and their mechanism of action have yet to be identified. Empirical use of artificial oocyte activation (AOA) methods has shown initial success in helping patients overcome TFF. The AOA methods attempt to raise calcium levels after fertilization, but the efficacy and safety of these AOA methods are still in early stages of addressing TFF. Additional information about calcium oscillatory patterns and the effects of AOA in human ART may allow the prevention of TFF or allow treatment of TFF patients effectively and safely.


Data analysis of vascular surgery instrument trays yielded large cost and efficiency savings.
Surgical procedures account for 50% of hospital revenue and ∼60% of operating costs. On average, <20% of surgical instruments will be used during a case, and the expense for resterilization and assembly of instrument trays ranges from $0.51 to $3.01 per instrument. Given the complexity of the surgical service supply chain, physician preferences, and variation of procedures, a reduction of surgical cost has been extremely difficult and often ill-defined. A data-driven approach to instrument tray optimization has implications for efficiency and cost savings in sterile processing, including reductions in tray assembly time and instrument repurchase, repair, and avoidable depreciation. During a 3-month period, vascular surgery cases were monitored using a cloud-based technology product (OpFlow, Operative Flow Technologies, Raleigh, NC) as a part of a hospital-wide project. Given the diversity of the cases evaluated, we focused on two main vascular surgery trays: vascular and aortic. An assessment was performed to evaluate the exact instruments used by the operating surgeons across a variety of cases. The vascular tray contained 131 instruments and was used for the vast majority of vascular cases, and the aortic tray contained 152 instruments. Actual instrument usage data were collected, a review and analysis performed, and the trays optimized. During the 3-month period, 168 vascular surgery cases were evaluated across six surgeons. On average, the instrument usage per tray was 30 of 131 instruments (22.9%) for the vascular tray and 19 of 152 (12.5%) for the aortic tray. After review, 45.8% of the instruments were removed from the vascular tray and 62.5% from the aortic tray, for 1255 instruments removed from the versions of both trays. An audit was performed after the removal of instruments, which showed that none of the removed instruments had required reinstatement. The instrument reduction from these two trays alone yielded an estimated costs savings of $97,781 for repurchase and $97,444 in annual resterilization savings. Annually, the removal of the instruments is projected to save 316.2 hours of personnel time. The time required for operating room table setup decreased from a mean of 7:44 to 5:02 minutes for the vascular tray (P < .0001) and from 8:53 to 4:56 minutes for the aortic tray (P < .0001). Given increasing cost constraints in healthcare, sterile processing remains an untapped resource for surgical expense reduction. A comprehensive data analytics solution provided the ability to make informed decisions in tray management that otherwise could not be reliably performed.


Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone.
A 76 year-old woman with a history of coronary artery bypass grafting and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The concentration of serum potassium was high, and normal sinus rhythm was restored after correction of the serum potassium level. The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor. This case is a good example of electrolyte imbalance causing acute life-threatening cardiac events. Clinicians should be alert to the possibility of hyperkalemia, especially in elderly patients using ACE/ARB in combination with potassium sparing agents and who have mild renal disturbance.


Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.
DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival.


Cultural aspects in the management of inborn errors of metabolism.
European Health Care Systems have not yet accommodated both previous and current migration waves. Children from immigrant families, especially children with chronic conditions, are particularly affected from the shortcomings in medical care. One condition, phenylketonuria (PKU), is an inborn error of metabolism (IEM) which results in intellectual disability unless treated with a lifelong phenylalanine (Phe) restricted diet. In our PKU clinic, patients from families who previously had emmigrated from the geographic area of Turkey to Austria, exhibited worse blood Phe control and cognitive development than comparable patients from native Austrian families. Using structured and semi-structured interviews, questionnaires, and illness narratives, we identified language, psychosocial, economic, educational and cultural barriers as factors influencing adherence to treatment. Our findings led us to conclude that access to interpreter services, exploration of the socio-cultural background and of family ecology, as well as bi-directional communication and medical decision making according to the "best interest of the child" principle, may improve outcomes in patients requiring complex treatment and care.


Genetic approaches to crop improvement: responding to environmental and population changes.
Crop production is threatened by global climate change, and recent demands for crops to produce bio-fuels have started to affect the worldwide supply of some of the most important foods. How can we support a growing human population in such circumstances? One potential solution is the improvement of crops to increase yield from both irrigated and non-irrigated lands, and to create novel varieties that are more tolerant to environmental stresses. Recent progress has been made in the isolation and functional analyses of genes controlling yield and tolerance to abiotic stresses. In addition, promising new methods are being developed for identifying additional genes and variants of interest and putting these to practical use in crop improvement.


Immediate neurocognitive effects of concussion.
To prospectively measure the immediate neurocognitive effects and early course of recovery from concussion and to examine the effects of loss of consciousness (LOC) and posttraumatic amnesia (PTA) on the severity of neurocognitive impairment immediately after concussion. A sports-related concussion research model was used to allow prospective immediate evaluation of concussion. A total of 2385 high school and college football players were studied. Ninety-one players (3.8%) sustained concussions during the study. A brief neurocognitive and neurological screening measure, the Standardized Assessment of Concussion, was used to assess cognitive functioning before the football season, immediately after injury, and 15 minutes, 48 hours, and 90 days after injury. Standardized Assessment of Concussion scores immediately after concussion were significantly lower than the preseason baseline score and the noninjured population baseline mean, even for injured subjects without LOC or PTA. Subjects with LOC were most severely impaired immediately after injury, whereas those without LOC or PTA were least impaired. Significant impairment was also detected 15 minutes after injury, but all three groups returned to baseline levels of cognitive functioning within 48 hours. These findings are the first to demonstrate not only that a gradient of increasing concussion severity is represented by PTA and LOC but also that measurable neurocognitive abnormalities are evident immediately after injury without PTA or LOC.


Rural versus metropolitan comparison of processes of care in the community-based management of TIA and minor stroke in Australia (an analysis from the INSIST study).
To compare processes of care and clinical outcomes of community-based management of TIAs and minor strokes (TIAMS) between rural and metropolitan Australia. Inception cohort study between 2012 and 2016 with 12-month follow-up after index event (sub-study of INSIST). Hunter and Manning valley regions of New South Wales, within the referral territory of the John Hunter Hospital Acute Neurovascular Clinic (JHHANC). Consecutive patients of 16 participating general practices, presenting with possible TIAMS to either primary or secondary care. Processes of care (referrals, key management processes, time-based metrics) and clinical outcomes. Of 613 participants with possible TIAMS who completed the baseline interview, 298 were adjudicated as having TIAMS (119 from rural, 179 from metropolitan). Mean age was 72.3 years (SD, 10.7) and 127 (43%) were women. Rural participants were more likely to be managed solely by a general practitioner (GP) than metropolitan participants (34% v 20%) and less likely to be referred to a JHHANC specialist (13% v 38%) or have brain magnetic resonance imaging (MRI) [24% v 51%]. Those rural participants who were referred, also waited longer (both p < 0.001). Recurrent stroke, myocardial infarction and death at 12 months were not significantly different between rural and metropolitan participants. Although TIAMS prognosis in rural settings where solely GP care is common is very good, the processes of care in such areas are inferior to metropolitan. This suggests there is further scope to support rural GPs to optimise care of TIAMS patients.


Rehabilitative ultrasound measurement of trapezius muscle contractile states in people with mild shoulder pain.
The utility of rehabilitative ultrasound imaging (RUSI) for assessing trapezius muscle contractile characteristics was investigated by examining whether muscle thickness changes during contraction (CT) differed between people with and without mild shoulder pain. In 18 subjects with mild shoulder pain (aged 28±8 years) and 18 matched controls, trapezius muscle thickness change was measured in prone at rest at 0° and during isometric CTs at 90° and 120° of shoulder abduction. Images were taken at four sites using a real-time ultrasound scanner (7-MHz linear transducer, 40 mm footprint). Percentage change in muscle thickness from rest was calculated. Differences between painful and non-painful shoulders and participant groups were examined by analysis of variance (ANOVA) and t-tests. There were no significant differences between groups or sides in trapezius muscle thickness change during CT. There was no significant difference in trapezius muscle resting thickness (RT) between painful and non-painful shoulders in the same subjects. Contractile ability of the trapezius muscle, assessed using RUSI was not impaired in subjects with mild shoulder pain during the test manoeuvres used. Further research is warranted involving patients with different severity of symptoms, using other test manoeuvres before RUSI can be advocated for assessing scapular muscle dysfunction.


Ginkgo biloba promotes short-term retention of spatial memory in rats.
This study examines possible interactions between exposure to Ginkgo biloba extract and enriched environments on the acquisition and retention of spatial learning following massed and spaced trials. After 4 weeks of exposure to either ginkgo or vehicle, 8-week-old rats were tested using a Morris Water Maze in either massed or spaced trials. While ginkgo did not have an effect on maze acquisition or long-term retention, it did promote short-term retention of spatial memory. Following reversal training, ginkgo promoted short-term retention for two groups but impaired retention for a third. These results suggest that ginkgo has powerful effects on short-term retention that vary with training conditions.


Polynitro-acetone, dimethyl ether, and dimethylamine: a series of potential green and powerful oxidants for propellants.
With the purpose of searching novel, green and energetic oxidants, polynitro-acetone, polynitro-dimethyl ether, and polynitro-dimethylamine are designed as potential powerful oxidants and energetic materials in this work. Their optimized molecular geometries and electronic structures are calculated using density functional theory at m062x/6-311G++(d,p) level. Based on these results, heat of formation (HOF), detonation energy (Q), detonation velocity (D), and detonation pressure (P) are further evaluated. It is found that the oxygen-rich and chlorine-free compounds with 5 to 6 NO2 groups in molecule can be used as the potential energetic oxidants with high oxygen balance, while those with 3 to 4 NO2 groups are suitable for high-density energetic materials. Furthermore, stability correlations of all the compounds are established according to calculated bond order, natural bond orbital (NBO), bond dissociation enthalpies (BDE), and energy gaps (ΔELUMO-HOMO). Finally, burning rate is also calculated to show their potential application as oxidants in propellants. Graphical abstract.


The metabolic consequences of adrenergic blockade: a reveiw.
The effects in man of adrenergic blocking agents on plasma insulin, glucagon, growth hormone, and lipid metabolism are reviewed. Whereas basal insulin may be slightly inhibited by beta- and enhanced by alpha-adrenergic blockade, more marked suppression may be achieved under circumstances of high exogenous or endogenous catecholamine stimulation. The relative effects of beta1 or combined beta 1 and beta2 blockers in man are unknown. Glucagon release is probably provoked by beta- and inhibited by alpha-stimulation in man. Muscle glycogenolysis is inhibited by propranolol, and under situations of hepatic glycogen depletion, clinical hypopglycemia may occur. This may also account for the failure of significant hyperglycemia to be observed in short-term experiments on fasting subjects in whom insulin release may be suppressed and glucagon release enhanced. Growth-hormone release is enhanced by beta-adrenergic blockade. Free fatty acid formation in vivo is inhibited by intravenous beta blockade, but the effects of oral administration on triglyceride production and lipoprotein profiles remain uncertain. The inter-relationships between the effects of adrenergic blockade at different sites of hormone and substrate release are unclear but may have important consequences in alteration in carbohydrate tolerance and lipid metabolism. The relative effects of beta-blocking drugs with differing specificity must be determined.


Building an ontology of adverse drug reactions for automated signal generation in pharmacovigilance.
Automated signal generation in pharmacovigilance implements unsupervised statistical machine learning techniques in order to discover unknown adverse drug reactions (ADR) in spontaneous reporting systems. The impact of the terminology used for coding ADRs has not been addressed previously. The Medical Dictionary for Regulatory Activities (MedDRA) used worldwide in pharmacovigilance cases does not provide formal definitions of terms. We have built an ontology of ADRs to describe semantics of MedDRA terms. Ontological subsumption and approximate matching inferences allow a better grouping of medically related conditions. Signal generation performances are significantly improved but time consumption related to modelization remains very important.


Impact of biopsy on the accuracy of endorectal ultrasound staging of rectal tumors.
Endorectal ultrasound is a well-established method for the preoperative staging of rectal tumors. This prospective study was performed to establish whether obtaining a biopsy before endorectal ultrasound has an influence on staging accuracy. Between 1990 and 2003, a total of 333 rectal tumors were examined preoperatively by using endorectal ultrasound. All patients underwent rectal resection, and the specimens were sent for histologic evaluation. Thirty-three were not biopsied, the remaining at various times before endorectal ultrasound. The chi-squared test or Fisher's exact test were used for statistical analysis to compare the accuracies. The overall staging accuracy was 71 percent but differed significantly (P = 0.004) between the groups as a function of time elapsed since biopsy. The best results were seen in tumors that were not biopsied before endorectal ultrasound, which were correctly staged in 85 percent of the cases. The least accurate staging (53 percent) was noted when endorectal ultrasound was performed in the third week after biopsy, mostly as a result of overstaging. Biopsy did not have a significant effect on nodal staging. Biopsy before endorectal ultrasound significantly affects its accuracy. To achieve the most accurate staging, biopsy should be performed after endorectal ultrasound. Endorectal ultrasound staging performed in the first week after biopsy is the second best option but should be interpreted with caution in the second or third week.


Synergistic co-delivery of diacid metabolite of norcantharidin and ABT-737 based on folate-modified lipid bilayer-coated mesoporous silica nanoparticle against hepatic carcinoma.
Diacid metabolite as the stable form of norcantharidin (DM-NCTD) derived from Chinese blister beetle (Mylabris spp.). The previous studies reported that DM-NCTD could enhance ABT-737-triggered cell viability inhibition and apoptosis in hepatocellular carcinoma (HCC) cell lines. To translate this synergistic therapy into in vivo anticancer treatment, a folate receptor-targeted lipid bilayer-supported chlorodimethyloctadecylsilane-modified mesoporous silica nanoparticle (FA-LB-CHMSN) with DM-NCTD loaded in CHMSN and ABT-737 in lipid bilayer was prepared, which could promote the cancer cell uptake of the drugs through folate receptor-mediated endocytosis. The structure and the properties of the nanoparticle were evaluated. FA-LB-CHMSN with DM-NCTD/ABT-737 loaded induced apparent tumor cell apoptosis and showed remarkably tumor inhibition in H22 tumor-bearing mice model, with significant cellular apoptosis in the tumor and no obvious toxicity to the tissues. We expect that this nanoparticle could be of interest in both biomaterial investigations for HCC treatment and the combination of chemotherapeutic drugs for synergistic therapies.


EppA, a putative substrate of DdERK2, regulates cyclic AMP relay and chemotaxis in Dictyostelium discoideum.
The mitogen-activated protein kinase DdERK2 is critical for cyclic AMP (cAMP) relay and chemotaxis to cAMP and folate, but the details downstream of DdERK2 are unclear. To search for targets of DdERK2 in Dictyostelium discoideum, 32PO4(3-)-labeled protein samples from wild-type and Dderk2- cells were resolved by 2-dimensional electrophoresis. Mass spectrometry was used to identify a novel 45-kDa protein, named EppA (ERK2-dependent phosphoprotein A), as a substrate of DdERK2 in Dictyostelium. Mutation of potential DdERK2 phosphorylation sites demonstrated that phosphorylation on serine 250 of EppA is DdERK2 dependent. Changing serine 250 to alanine delayed development of Dictyostelium and reduced Dictyostelium chemotaxis to cAMP. Although overexpression of EppA had no significant effect on the development or chemotaxis of Dictyostelium, disruption of the eppA gene led to delayed development and reduced chemotactic responses to both cAMP and folate. Both eppA gene disruption and overexpression of EppA carrying the serine 250-to-alanine mutation led to inhibition of intracellular cAMP accumulation in response to chemoattractant cAMP, a pivotal process in Dictyostelium chemotaxis and development. Our studies indicate that EppA regulates extracellular cAMP-induced signal relay and chemotaxis of Dictyostelium.


Alpha-adrenergic responsiveness in rat isolated perfused heart after abdominal aortic coarctation.
Chronic isoproterenol pre-treatment, a well-known model of compensatory hypertrophy associated with cardiac beta-adrenoceptor desensitization, enhances the inotropic response to phenylephrine in rat isolated perfused hearts, supporting the hypothesis that myocardial alpha-adrenoceptor stimulation contributes to the maintenance of myocardial performance in situations in which cardiac beta-adrenoceptor function is compromised. To further corroborate this hypothesis, the effects of abdominal aortic coarctation on cardiac alpha-adrenergic responsiveness were investigated in Langendorff heart preparations. Abdominal aortic coarctation causes cardiac hypertrophy (21%) as shown by a significant increase in the ratio of ventricular dry weight to bodyweight. In preparations from hypertrophied rats, both maximum increases in left ventricular systolic pressure and heart rate elicited by isoproterenol (10(-12) to 10(-4) M) were significantly reduced (the isoproterenol concentration producing 50% of the maximum positive inotropic and chronotropic responses was enhanced almost 21- and 2-fold, respectively). However, the positive inotropic response to phenylephrine (10(-12) to 10(-4) M) remained unaffected following abdominal aortic coarctation, when compared with sham-operated rats. In preparations from both groups, phenylephrine infusion did not induce significant changes in heart rate. These results show that although abdominal aortic stenosis induced desensitization of cardiac beta-adrenoceptors, it did not enhance cardiac alpha-adrenoceptor responsiveness. This suggests that such an enhancement depends on the experimental model used to induce cardiac hypertrophy associated with desensitization of cardiac beta-adrenoceptors.


Recent evolution of uniform trichromacy in a New World monkey.
Until recently, New World primates were found to have a single M/L photopigment gene on the X-chromosome. This arrangement limits males to dichromatic, or monochromatic color vision. Only females who were heterozygous for the M/L gene were trichromatic. Recently, an exception has been discovered. Male howler monkeys appear to have more than one M/L pigment gene, and both genders are uniformly trichromatic. We characterized promoter regions corresponding to two M/L pigment genes in howlers. Comparison of DNA sequences with those of humans and three species of New World primate suggest a recent and independent acquisition of a second M/L gene locus in the howler.


Endothiopeptide inhibitors of HIV-1 protease.
Endothiopeptide inhibitors of HIV-1 protease were synthesized by chemical and enzymatic methods to individually replace each backbone amide bond in 1 with a thioamide-linkage. Interestingly, agent 7, which contains a thioamide-linkage between the P2' and P3' positions of 1, was the most potent, competitive inhibitor of HIV-1 protease with a Ki of 3.4 microM.


Adult health behaviors over the life course by sexual orientation.
We estimated differences in health behaviors among adults by sexual orientation. We pooled 4 years of data (2001, 2003, 2005, and 2007) from the California Health Interview Survey. We estimated the frequency of smoking, alcohol use, healthy dietary behaviors, physical activity, and health care utilization, and we used logistic regression modeling to determine the odds of each behavior with increasing age and for 2 age groups: younger than 50 years and 50 years old or older. At any adult age, lesbians had greater odds of smoking and binge drinking than did heterosexual women, and gay and bisexual men had greater health care utilization than did heterosexual men. Other risk behaviors differed with age. Some behavioral change interventions should target lesbians, gays, and bisexuals at all ages, whereas other interventions should specifically target individuals at younger ages.


Pathophysiology of cardiac hypertrophy and failure of human working myocardium: abnormalities in calcium handling.
Abnormal intracellular calcium ([Ca2+]i) handling appears to be a major cause of both systolic and diastolic dysfunction in animals and human beings with hypertrophy and/or heart failure. We utilized the bioluminescent calcium indicator aequorin to examine the cyclical variations in intracellular calcium levels during isometric contractions. Studies of ventricular muscle from patients with end-stage heart failure exhibited three physiologic findings not seen in preparations taken from normal hearts including: 1) abnormalities in calcium handling; 2) deficient production of cyclic AMP; and 3) a reversed force-frequency relationship. These observations have important implications with regard to the pathogenesis and therapeutics of heart failure in man.


Critical evaluation of sampling and gas chromatographic analysis of halocarbons and other organic air pollutants.
Problems connected with the analysis of ultra-trace amounts of halocarbons in air are discussed in terms of trapping procedures, interferences and chromatographic columns. A suitable column for the qualitative and quantitative analysis of C1-C2 halocarbons is described, and examples of applications are given. High-efficiency micropacked columns have been used for the analysis of hydrocarbons in the open atmosphere.


Induction of chromosome aberrations by chemical mutagens in neural ganglia of Drosophila melanogaster.
Chromatid aberrations induced by various concentrations of bleomycin, cyclophosphamide and mitomycin C were analyzed in neural ganglia of third-instar larvae of Drosophila melanogaster. A clear dose response was observed with increasing dose after treatment with bleomycin and mitomycin C, whereas no effect was observed after treatment with cyclophosphamide. A comparison with published data for the induction of sex-linked recessive lethals showed that, at least for the 3 drugs tested, the use of both tests eliminates false negatives and might comprise a useful procedure for testing mutagenicity in Drosophila.


The effect of labour on prolactin and cortisol concentrations in the mother and the fetus.
Concentrations of prolactin and cortisol were determined in maternal and umbilical cord serum of women delivered by elective Caesarean section and by vaginal delivery. There was no difference in the concentration of prolactin in the two groups of women. Similarly, cord blood prolactin concentrations were not significantly different in the two groups. Cortisol concentrations in the women undergoing Caesarean section were similar to the vaginal delivery group before the onset of labour. However, there was a significant increase in cortisol concentration at delivery following labour. The cord blood cortisol concentration was significantly higher in the neonates delivered vaginally, and it correlated with the maternal cortisol concentration at delivery. The relevance of these findings is discussed.


MetExtract: a new software tool for the automated comprehensive extraction of metabolite-derived LC/MS signals in metabolomics research.
Liquid chromatography-mass spectrometry (LC/MS) is a key technique in metabolomics. Since the efficient assignment of MS signals to true biological metabolites becomes feasible in combination with in vivo stable isotopic labelling, our aim was to provide a new software tool for this purpose. An algorithm and a program (MetExtract) have been developed to search for metabolites in in vivo labelled biological samples. The algorithm makes use of the chromatographic characteristics of the LC/MS data and detects MS peaks fulfilling the criteria of stable isotopic labelling. As a result of all calculations, the algorithm specifies a list of m/z values, the corresponding number of atoms of the labelling element (e.g. carbon) together with retention time and extracted adduct-, fragment- and polymer ions. Its function was evaluated using native (12)C- and uniformly (13)C-labelled standard substances. MetExtract is available free of charge and warranty at http://code.google.com/p/metextract/. Precompiled executables are available for Windows operating systems. Supplementary data are available at Bioinformatics online.


Current status of intravesical chemotherapy trials in the EORTC Urological Group. An overview.
The EORTC Urological Group is one of the 31 clinical groups and working parties within the European Organization for Research and Treatment of Cancer (EORTC). Intravesical chemotherapy has been used as chemoresection or chemoprophylaxis. Chemoresection has mainly been utilized in phase II studies to demonstrate ablation of existing disease and to study the mechanism of drug action. These studies are usually performed by individual members to obtain relevant information for the preparation of randomized trials. One example is a phase II chemoresection study with 4'-epi-doxorubicin (EPR). The EORTC GU Group extended its phase II trials to study remission in patients with primary carcinoma in situ. A new concept introduced in the prospective, randomized phase III trials includes the evaluation of chemoresection of a marker lesion as a prognostic factor in long-term prophylactic treatment. Chemoprophylaxis in the phase III trials aims to study the disease-free period, the recurrence rate and the long-term survival. So far, a series of five phase III trials, totaling more than 2,000 patients, demonstrated the efficacy of chemoprophylaxis to reduce tumor recurrence rates. The variation in the results of the different trials are due more to the prognostic factors (characteristics of the tumors) than to the related efficacy of the chemoprophylactic drugs. The selection of currently employed drugs, Mitomycin C, Epirubicin and BCG, is based on reported results, lack of toxicity, and drug availability in Europe. The data collected will be of great importance to determine the optimal clinical management of superficial bladder cancer.


Effect of morphine on locomotor activity and striatal monoamine metabolism in nicotine-withdrawn mice.
Evidence for an interaction between nicotine and morphine has been found in several studies. In the present study mice withdrawn from a 7-week oral nicotine treatment were administered morphine, following which their locomotor activities were recorded and the concentrations of dopamine, 5-hydroxytryptamine (5-HT), noradrenaline and their metabolites were measured in the caudate putamen (CPu) and nucleus accumbens (NAc). For comparison, the effect of cocaine on locomotor activity was studied in mice withdrawn from nicotine. Morphine (15 mg/kg s.c.) enhanced locomotor activity significantly more in the nicotine-withdrawn mice than in the controls, whereas cocaine (20 mg/kg i.p.) stimulated the locomotor activity similarly in the nicotine-withdrawn and in the control mice. Morphine (10 mg/kg s.c.) elevated dopamine and 5-HT metabolites to the same degree in the NAc of the nicotine-withdrawn and the control mice. However, in the CPu morphine enhanced the metabolism of dopamine and also that of 5-HT in the nicotine-withdrawn mice but not in the controls. In addition, the basal concentrations of dopamine metabolites were reduced in the CPu of the nicotine-withdrawn mice. Thus, the enhancement of morphine-induced locomotor activation in the nicotine-withdrawn mice could be related to nicotine-induced changes in the regulation of the nigrostriatal dopaminergic and serotonergic systems.


Endoscopic fistulotomy (EFT) for parapapillary choledochoduodenal fistula.
Up to now, surgery was the only possible treatment for choledochoduodenal fistulas, which are seen more often in Japan than in Europe. This paper presents the value and effect of endoscopic fistulotomy (EFT) as an alternative treatment in those cases. Parapapillary choledochoduodenal fistulas are abserved usually on the longitudinal fold of the papilla or on its oral side. The papillotome is inserted into the common bile duct through the orifice of the duodenal papilla, then the wall between its orifice and the fistula is cut to open widely the distal portion of the choledochus. EFT was performed successfully in 7 cases. The procedure led to a wide open stoma of the distal common bile duct with free bile outflow. Residual stones, a common occurrence in cases of parapapillary choledochoduodenal fistulas, may pass spontaneously after EFT or can be removed with a basket catheter. In cases of parapapillary choledochoduodenal fistula, EFT is a reliable method, especially in high-risk patients, and an alternative to surgical treatment.


The spatiotemporal transmission dynamics of COVID-19 among multiple regions: a modeling study in Chinese provinces.
Current explosive outbreak of COVID-19 around the world is a complex spatiotemporal process with hidden interactions between viruses and humans. This study aims at clarifying the transmission patterns and the driving mechanism that contributed to the COVID-19 prevalence across the provinces of China. Thus, a new dynamical transmission model is established by an ordinary differential system. The model takes into account the hidden circulation of COVID-19 virus among/within humans, which incorporates the spatial diffusion of infection by parameterizing human mobility. Theoretical analysis indicates that the basic reproduction number is a unique epidemic threshold, which can unite infectivity in each region by human mobility and can totally determine whether COVID-19 proceeds among multiple regions. By validating the model with real epidemic data in China, it is found that (1) if without any intervention, COVID-19 would overrun China within three months, resulting in more than 1.1 billion clinical infections and 0.2 billion subclinical infections; (2) high frequency of human mobility can trigger COVID-19 diffusion across each province in China, no matter where the initial infection locates; (3) travel restrictions and other non-pharmaceutical interventions must be implemented simultaneously for disease control; and (4) infection sites in central and east (rather than west and northeast) of China would easily stimulate quick diffusion of COVID-19 in the whole country. The online version supplementary material available at 10.1007/s11071-021-07001-1.


Cysticercosis of slaughtered cattle in northwestern Ethiopia.
The occurrence of cysticercosis due to Taenia saginata in cattle slaughtered for meat in Amhara National Regional State, northwestern Ethiopia between September 2005 and February 2007 was investigated. Routine meat inspection of various organs of 4456 cattle in eight abattoirs of this region showed that 824 (18.49%) were infected with Cysticercus bovis. The occurrence rate did not vary significantly from abattoir to abattoir (P>0.5). The tongue, masseter muscles, heart muscles, triceps muscles and thigh muscles were the main predilection sites of the cysts. Of 4102 male cattle, examined, 768 (18.72%) had cysts of C. bovis while 56 (15.82%) of the 354 female animals investigated were infected. The animals slaughtered were all adults. No significant difference in occurrence was recorded between the sexes. Monthly occurrence of the cysts in the animals revealed a rise of infected animals during the dry season.


Effects of heavy pollution in different water bodies on male rainbow trout (Oncorhynchus mykiss) reproductive health.
This research aimed to investigate the influence of heavy metals on the reproductive health of rainbow trout (Oncorhynchus mykiss) captured from two locations, Verinag (S1) and Panzath (S2). Sixty (n. 60) mature rainbow trout samples (30 from each site) with body weights ranging from 400 to 650 g were collected from Verinag hatchery, which was less polluted (S1), and Panzath hatchery, which was more polluted (S2). The findings revealed significant differences between the two sites, S1 (less polluted) and S2 (more polluted), as well as significant variations within the tissues. Iron (Fe) and Zinc (Zn) were found to be highest in sampling water as well as in fish tissues sampled from S2 sites. Similarly, concerning S1 captured fishes, histopathological examination of testes from S2 captured fish was found. Testicular abnormalities that included disorganization of the seminiferous tubules, reduction in the number of germ cells (sperm cells, spermatozoa), vacuolization, and large empty areas in the seminiferous epithelium were found. In testicular cells, the frequency of apoptotic cells collected from S2 water increased significantly (P < 0.05). SOD, catalase, and glutathione peroxidase activity increased in S1 captured fishes but decreased in S2 captured fishes. MDA levels gradually increased in S2 captured fish, and the degree of heavy metal stress was positively correlated (P < 0.05). In male rainbow trout, testosterone and 11-ketotestosterone levels increased substantially in S1 captured fishes. While the fatty acids of testes in S2 fishes decreased with respect to S1 fishes. In conclusion, S2 captured fish suffered more damage due to heavy metals including cellular damage, apoptosis, oxidative damage, and altered steroid hormones when compared to fish from S1 waters.


Antagonism of endogenous opioids modulates memory processing.
The studies reported here demonstrate that opioid antagonism enhances memory in two classes of animals viz. Aves and Mammalia. In mice, immediate posttraining administration of naloxone produces a time-dependent improvement in retention tested one week later. This effect is stereospecific. As naloxone was approximately 1000-fold more potent when administered intracerebroventricularly compared to subcutaneously, it appears that it produces its effect within the central nervous system. Pretest administration of naloxone, at a dose that failed to alter acquisition, also improved test performance, suggesting that naloxone also improved recall. Similar improvement in retention was demonstrated with the more potent opioid antagonist, nalmefene, at a 500-fold lower dose. The dose response to naloxone in both the mouse and the chick and to nalmefene in the mouse had the characteristics of an inverted U, with high doses either being ineffective or suppressing memory retention. In mice, naloxone demonstrated anti-amnestic properties against both anisomycin, a protein synthesis inhibitor, and scopolamine, an acetylcholine receptor blocker. Administration of beta-funaltrexamine (B-FNA) 72 h prior to training did not alter acquisition but did enhance retention. In studies where the mu-opioid receptor was blocked with B-FNA, naloxone was unable to enhance retention. B-FNA failed to impair the memory enhancing properties of arecoline, fluoxetine or clonidine. This demonstrates specificity of the B-FNA ability to prevent naloxone from enhancing memory and suggests that the opioid antagonist effects on memory are mediated by the mu-receptor.


Depression in alcoholics by the NIMH-Diagnostic Interview Schedule and Zung Self-Rating Depression Scale.
Depression was prominent among 40 alcoholics in an alcohol treatment program. Untreated depression may increase risk for relapse to problem drinking. The structured diagnostic interview schedules, DIS and Zung, showed good agreement and were effective instruments in the detection of depression in alcoholics.


Privileged communication--talking with a dying adolescent.
For an adolescent who is dying, the opportunity to experience control, autonomy, and a feeling of belonging eases uncertainty and turmoil.


Physical, chemical, and sensory properties of water kefir produced from Aronia melanocarpa juice and pomace.
Water kefir is widely consumed all over the world due to its potential health benefits. The aim of this current study was to compare non-fermented juice and fermented beverage of water kefir produced from Aronia melanocarpa juice and pomace in terms of chemical, physical and sensory quality as well as valorisation of pomace in the production of water kefir. When compared to water kefir made with aronia juice, less reduction in total phenolic content (TPC), total flavonoid content (TFC) and total anthocyanin content (TAC) was observed in samples made with aronia pomace during the fermentation process. Similarly, greater antioxidant activity was demonstrated in water kefir made with aronia pomace than juice. Based on sensory evaluation, no difference was found in overall acceptability, taste, aroma/odor, and turbidity of water kefir made with aronia pomace before and after fermentation. Results indicated that aronia pomace has potential in water kefir production.


The TAED/H2O2/NaHCO3 system as an approach to low-temperature and near-neutral pH bleaching of cotton.
A low-temperature and near-neutral pH bleaching system was conceived for cotton by incorporating TAED, H2O2 and NaHCO3. The TAED/H2O2/NaHCO3 system was investigated and optimized for bleaching of cotton using a central composite design (CCD) combined with response surface methodology (RSM). CCD experimental data were fitted to create a response surface quadratic model (RSQM) describing the degree of whiteness of bleached cotton fabric. Analysis of variance for the RSQM revealed that temperature was the most significant variable, followed by [TAED] and time, while [NaHCO3] was insignificant. An effective system was conducted by adding 5.75 g L(-1) TAED together with H2O2 and NaHCO3 at a molar ratio of 1:2.4:2.8 and applied to bleaching of cotton at 70 °C for 40 min. Compared to a commercial bleaching method, the TAED/H2O2/NaHCO3 system provided cotton with comparable degree of whiteness, slightly inferior water absorbency and acceptable dyeability, but had competitive advantage in protecting cotton from severe chemical damage in bleaching.


Coherent encoding of subjective spatial position in visual cortex and hippocampus.
A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brain's visual and navigational systems are known to interact5,6, and signals related to position in the environment have been suggested to appear as early as in the visual cortex6,7. Here, to establish the nature of these signals, we recorded in the primary visual cortex (V1) and hippocampal area CA1 while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly at those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position rather than the other. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animal's subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animal's position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animal's subjective estimate of position, inferred from the animal's licks, better than its actual position. When animals licked in a given location-whether correctly or incorrectly-neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are controlled by navigational signals, which are coherent with those encoded in hippocampus and reflect the animal's subjective position. The presence of such navigational signals as early as a primary sensory area suggests that they permeate sensory processing in the cortex.


Two different secretion mechanisms in the inner ear's interdental cells.
Fixation with a mixture of tannic acid and glutaraldehyde reveals a darkly stained substance in the intercellular clefts between juxtapposed interdental cells, where it is included by pynocytotic vesicles. Over the interdental cells, similar-sized vesicles (35-45 nm) are present in clear spaces of the amorphous layer of the limbal portion of the tectorial membrane. Some images suggest that they may be secreted through small disruptions of the membrane of the interdental cells' microvilli. In addition, a TA-unstained, amorphous material is present inside both basal ducts and apical cavities of the interdental cells, thus suggesting another secretory route from the basal region of the interdental cells towards either the endolymph, or the tectorial membrane. These two secretion processes coexist in a single interdental complex, and the two secretion products may be involved in the turnover of the adult tectorial membrane and/or the secretion of some component of the endolymph.


Gastrin interferes with the differentiation of gastric pit cells and parietal cells.
Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known. To investigate the long-term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene-expressing mice showed serum gastrin levels of more than 600 pg/mL. Neither progastrin nor glycine-extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30-35-week-old transgenic mice were 30-50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K-ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo, specific gastrin binding sites were observed in the mid-glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells. These results suggest that long-term stimulation of gastrin increases the expression of CCK-B/gastrin receptors in the less-differentiated pit cells that are the main component of elongated gastric units, and lessens the well-differentiated characteristics of parietal cells.


Exploring the peripheral mechanisms of lower limb immobilisation on muscle function using novel electrophysiological methods.
To explore the effects of short-term immobilisation and subsequent retraining on peripheral nervous system (PNS) measures using two novel electrophysiological methods, muscle velocity recovery cycles (MVRC) and MScanFit motor unit number estimation (MUNE) alongside lower limb muscle strength, muscle imaging and walking capacity. Twelve healthy participants underwent 1-week of ankle immobilisation and 2-weeks of retraining. Assessments before and after immobilisation, and after retraining, included MVRC [muscle membrane properties; muscle relative refractory period (MRRP), early and late supernormality], MScanFit, MRI-scans [muscle contractile cross-sectional area (cCSA)], isokinetic dynamometry [dorsal and plantar flexor muscle strength], and 2-minute maximal walk test [physical function]. After immobilisation, compound muscle action potential (CMAP) amplitude reduced (-1.35[-2.00;-0.69]mV); mean change [95%CI]) alongside reductions in plantar (but not dorsal) flexor muscle cCSA (-124[-246;3]mm2), dorsal flexor muscle strength (isometric -0.06[-0.10;-0.02]Nm/kg, dynamicslow -0.08[-0.11;-0.04]Nm/kg, dynamicfast no changes), plantar flexor muscle strength (isometric -0.20[-0.30;-0.10]Nm/kg, dynamicslow -0.19[-0.28;-0.09]Nm/kg, dynamicfast -0.12[-0.19;-0.05]Nm/kg) and walking capacity (-31[-39;-23]m). After retraining, all immobilisation-affected parameters returned to baseline levels. In contrast, neither MScanFit nor MVRC were affected apart from slightly prolonged MRRP in gastrocnemius. PNS do not contribute to the changes observed in muscle strength and walking capacity. Further studies should include both corticospinal and peripheral mechanisms.


Changes in operative trends and short-term outcomes of surgery for congenital biliary dilatation in adults using real-world data: A multilevel analysis based on a nationwide administrative database in Japan.
We aimed to evaluate the operative trends and compare the short-term outcomes between open and laparoscopic surgery for congenital biliary dilatation (CBD) in adults using real-world data from Japan. Data from the Japanese Diagnosis Procedure Combination database on 941 patients undergoing surgery for CBD at 357 hospitals from April 1, 2016, to March 31, 2021, were analyzed. The patients were divided into two groups: open surgery (n = 764) and laparoscopic surgery (n = 177). We performed a retrospective analysis via a multilevel analysis of the short-term surgical outcomes and costs between open and laparoscopic surgery. The rate of laparoscopic surgery has been increasing annually and had almost doubled to 25% by 2021. There were no significant differences in the in-hospital mortality rate or postoperative morbidity between the two groups. The length of anesthesia was significantly longer in the laparoscopic than open surgery group (8.80 vs 6.16 hours, p < .001). The time to removal of the abdominal drain and length of hospital stay were significantly shorter in the laparoscopic than open surgery group (6.12 vs 8.35 days, p = .001 and 13.57 vs 15.79 days, p < .001, respectively). The coefficient for cost was 463 235 yen (95% confidence interval, 289 679-636 792) higher in laparoscopic than open surgery (p < .001). The short-term results were comparable between laparoscopic and open surgery for CBD. Further investigation is needed to validate our findings and long-term outcomes.


Phenotype-oriented anticoagulant therapy for sepsis: still a work in progress.
Coagulation disorders ranging from subtle changes in coagulation parameters to fatal disseminated intravascular coagulation (DIC) are common in septic patients. Coagulation activation is considered to be one of the most important factors contributing to multiple organ dysfunction syndrome (MODS) in sepsis. Anticoagulant therapy is, therefore, necessary to prevent MODS, but eligibility criteria remain controversial. Sepsis is a highly heterogeneous syndrome, which could explain the negative results of clinical studies on the treatment of sepsis. Recently, sepsis has been subdivided into several phenotypes with different therapeutic outcomes. At present, septic patients with dysfunctional coagulation expressed as increased D-dimer and fibrin/fibrinogen degradation products (FDPs) are considered to be candidates for anticoagulant therapy. In this review, we aimed to describe the features of different septic phenotypes. We also discuss factors that contribute to controversies in this area, and challenges in defining which septic phenotypes are good candidates for anticoagulant therapy.


Aggregation-Induced Dual-Phosphorescence from Organic Molecules for Nondoped Light-Emitting Diodes.
Aggregation-induced emission (AIE) is a beneficial strategy for generating highly effective solid-state molecular luminescence without suffering losses in quantum yield. However, the majority of reported AIE-active molecules exhibit only strong fluorescence, which is not ideal for electrical excitation in organic light-emitting diodes (OLEDs). By introducing various substituent groups onto the biscarbazole compound, a series of molecular materials with aggregation-induced phosphorescence (AIP) is designed, which exhibits two distinctly different phosphorescence bands and an absolute solid-state room-temperature phosphorescence quantum yield up to 64%. Taking advantage of the AIE feature, the AIP molecules are fabricated into OLEDs as a homogeneous light-emitting layer, which allows for relatively small efficiency roll-off and shows an external electroluminescence quantum yield of up to 5.8%, more than the theoretical limit for purely fluorescent OLED devices. The design showcases a promising strategy for the production of cost-effective and highly efficient OLED technology.


Structure--activity relationships of anesthetic ethers using molecular connectivity.
The structure--activity relationships in the anesthetic and toxic actions of 28 aliphatic ethers were simple functions of molecular connectivity indexes. These quantitative relationships are discussed briefly in the light of theories of the mechanism of action of general anesthetics.


Structure of a cyclin-dependent kinase from Giardia lamblia.
Giardia lamblia is the etiologic agent of giardiasis, a water-borne infection that is prevalent throughout the world. The need for new therapeutics for the treatment of giardiasis is of paramount importance. Owing to the ubiquitous nature of kinases and their vital importance in organisms, they are potential drug targets. In this paper, the first structure of a cyclin-dependent kinase (CDK) from G. lamblia (GlCDK; UniProt A8BZ95) is presented. CDKs are cell-cycle-associated kinases that are actively being pursued as targets for anticancer drugs as well as for antiparasitic chemotherapy. Generally, a CDK forms a complex with its associated cyclin. This CDK-cyclin complex is active and acts as a serine/threonine protein kinase. Typically, CDKs are responsible for the transition to the next phase of the cell cycle. Although the structure of GlCDK with its associated cyclin was not solved, the 1.85 Å resolution structure of apo GlCDK and a 2.0 Å resolution structure of GlCDK in complex with adenosine monophosphate are presented and the structural differences from the orthologous human CDK2 and CDK3 are discussed.


Reopenable clip-over-the-line method for closing large mucosal defects following gastric endoscopic submucosal dissection: Prospective feasibility study.
Large mucosal defects following gastric endoscopic submucosal dissection (ESD) cause postoperative bleeding. To address this limitation and ensure closure of large mucosal defects, we developed the reopenable clip-over-the-line method (ROLM) using a reopenable clip and nylon line. The purpose of this study was to evaluate the feasibility of the ROLM for closure of large mucosal defects following gastric ESD in a prospective, consecutive series of cases. We performed the ROLM on 50 consecutive patients with gastric mucosal defects at the Ise Red Cross Hospital and Mie Prefectural Shima Hospital. The time to complete the ROLM, numbers of clips and lines required, size of defect, and closure success rate were measured, and postoperative adverse events were recorded. In all, 50 lesions were included in this study period between July 2021 and March 2022. The success rates of defect closure and defect closure without submucosal dead space of the ROLM were both 100% (50/50), with a median ROLM time of 30 (range, 14-35) min and a median resected specimen major axis of 45 (range, 31-73) mm. The median number of reopenable clips used was 31 (range, 10-93). Following gastric ESD, two cases of post-ESD bleeding were observed during the follow-up periods. Our results suggest that ROLM is a feasible strategy for complete closure of mucosal defects post-ESD without submucosal dead space. Future comparative studies with post-ESD bleeding rate as the main outcome are desirable to evaluate the efficacy of ROLM.


Conditional hepatocarcinogenesis in mice expressing SV 40 early sequences.
We closely mimicked the in vivo setting in which sporadic hepatocarcinoma occurs by establishing a transgenic mouse model carrying regulatable SV40 early sequences under the control of the regulatory sequences of the human antithrombin III gene that confer hepatic expression. In this system, floxed dormant oncogenic sequences became functional after excision due to adenoviral expression of Cre recombinase or the stable transgenic expression in liver of a tamoxifen-inducible Cre. Hepatic oncogene expression was switched on by both methods, leading to the development of hepatocellular carcinoma. This model could be useful for investigating the key steps of the preneoplastic process, to identify suitable targets for the testing of new therapies.


Restraining Erwinia virulence by expression of N-acyl homoserine lactonase gene pro3A-aiiA in Bacillus thuringiensis subsp leesis.
To widen the biological control function of a genetically modified Bacillus thuringiensis subsp leesis strain BMB-005, an acyl homoserine lactonase (AHL lactonase) gene aiiA transcribed by the promoter of insecticidal crystal protein coding gene cry3A, was transformed into strain BMB-005. The amount of AHL lactonase protein produced by transformant BMB821A was 2.4-fold more than that produced by BMB-005. AHL-degradation assay showed that transformant BMB821A could degrade more AHLs molecules than the original strain BMB-005. The result of Erwinia carotovora pathogenicity test showed that the parental strain BMB-005 had no restraint of Erwinia infection, but the transformants exhibited strong restraint of E. carotovora infection on potato slices and cactus stems. Insecticidal bioassay against lepidopteran Spodoptera exigua showed that both strain BMB-005 and transformant BMB821A were toxic to S. exigua. The toxicity of transformant BMB821A (LC(50) was 3.8) was a little attenuated comparing with the toxicity of the original strain BMB-005 (LC(50) was 2.9). The B. thuringiensis strain BMB-005 has high toxicity against Helicoverpa armigera, Plutella xylostella, and S. exigua. This work provided new strategy for developing genetically engineered multi-functional B. thuringiensis strain that possesses insecticidal activity together with restraint of bacterial pathogenicity.


Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals.
MAP-kinase signaling pathways are activated by multiple extracellular stimuli. The specificity of activation and function of MAP-kinase signaling modules is determined, in part, by scaffold proteins that create multienzyme complexes. In Saccharomyces cerevisiae, two MAP-kinase-scaffold proteins have been identified. Recent studies of mammalian cells have also led to the identification of putative scaffold proteins. These scaffold proteins appear to facilitate MAP-kinase activation, in response to specific physiological stimuli, and to insulate the bound MAP-kinase module against activation by irrelevant stimuli. Scaffold proteins are therefore critical components of MAP-kinase modules and ensure signaling specificity.


Base-catalyzed hydrolysis of spectinomycin in aqueous solutions: Kinetics and mechanisms.
Hydrolysis plays an imperative role in the abiotic transformation process of antibiotics in aqueous solutions. However, little information is available on the hydrolysis process of spectinomycin (an aminocyclitol antibiotic). This study systematically investigated the spectinomycin hydrolysis kinetics and mechanisms under different pH via experiments and density functional theory (DFT) computation. Hydrolysis was first conducted in a pure water system under pH of 4.0-9.0 and temperature of 25 °C, 50 °C and 70 °C, respectively. Results showed that hydrolysis was highly dependent on pH and temperature. When pH > 6.0, spectinomycin hydrolysis was accelerated by the catalysis of OH-. Meanwhile, the hydrolysis rate increased with the elevation of temperature. Then, for the reference of the practical environment, the general base-catalyzed hydrolysis and mechanisms were studied under environmental pH 6.0-8.0 and 25 °C. DFT calculation demonstrated that base-catalyzed hydrolysis of spectinomycin could be more thermodynamically and kinetically favorable based on the lower Gibbs free energies of reaction and Gibbs free energies of activation. Further, instead of specific base catalysis (OH-), the general base catalysis (e.g., phosphate buffer) was also found to promote hydrolysis efficiency. The antibacterial activity and ecotoxicities of the hydrolysis product were analyzed to be lower than the precursor, thereby decreasing the environmental impact of spectinomycin.


Histological significance of hepatitis-like findings in biliary atresia: An analysis of 34 Japanese cases.
Hepatocellular injury including multinuclear changes are common histological features in biliary atresia (BA), as well as in neonatal hepatitis. To date, however, no reports have examined how those findings correlate with the prognosis of BA. We clarified the clinical implications of hepatitis-related changes in BA on histological analysis. We retrospectively reviewed 34 cases of BA treated over the past 30 years at Ibaraki Children's Hospital. Liver biopsy specimens during Kasai procedures were evaluated for hepatocyte multinuclear change, ballooning, and acidophilic body, hereby defined as hepatitis-like findings (HLF). Each finding was semi-quantitatively scored as 0-2, and their sum was defined as the HLF score, ranging from 0 to 6. We examined the correlation between HLF score and total bilirubin (T-Bil), direct bilirubin (D-Bil), and other liver function test results at the Kasai procedure, as well as 1 week, and 1, 3, and 6 months after the Kasai procedure. Subsequently, HLF score was compared between native liver survivors (NLS; n = 16) and non-NLS (n = 18) for long-term analyses. Hepatitis-like findings score except for aspartate aminotransferase (AST), had no correlation with the preoperative data. HLF score was positively correlated, however, with T-Bil, D-Bil, and AST at 1 week and 1 month after the Kasai procedure (1 week: P = 0.009, 0.023, and 0.019; 1 month: 0.022, 0.019, and 0.013, respectively). HLF score was not significantly different between the NLS and non-NLS groups. Higher HLF score at Kasai procedure is an indicator of poor liver function at short-term follow up.


Simultaneous removal of carbamazepine and Cd(II) in groundwater by integration of peroxydisulfate oxidation and sulfidogenic process: The bridging role of SO42.
Heat-activated PDS oxidation (HAPO) has been widely used for in-situ chemical oxidation (ISCO) of micropollutants in groundwater, whereas the aesthetic demerit of additional SO42- production is largely overlooked. In this study, the sulfidogenic process is used to offset the aesthetic demerit, and the production of SO42- is then employed to recycle heavy metals. The innovative integration technology with PDS oxidation and sulfidogenic process via the bridging role of SO42- was reported to remove micropollutants and heavy metals in groundwater simultaneously. HAPO could completely degrade CBZ, producing 400 mg/L SO42- with the addition of 0.50 g/L PDS. Sulfate-reducing bacteria (SRB) utilize SO42- generated from HAPO as the electron acceptor in the sulfidogenic process, removing and recycling Cd(II) via the precipitation of CdS. The SRB tolerance experiment revealed the viability of PDS oxidation coupled with the sulfidogenic process via the bridging role of SO42-. Overall, the integration technology is a green and promising technology for simultaneous micropollutants removal and heavy metals recycling in groundwater.


CARD15 gene and the classification of Crohn's disease.
An insertion mutation at nucleotide 3020 (3020insC) in the CARD15 gene, originally reported as NOD2, has been strongly associated with Crohn's disease. The CARD15 G2722C missense mutation was also shown to be associated with this disease. We studied 130 Dutch Crohn's disease patients, with a median follow up of 9.2 years, in relation to the Vienna classification, and 152 ethnically matched healthy controls. We confirm reports that the CARD15 3020insC mutation increases the susceptibility to Crohn's disease, but we do not confirm this relationship for CARD15 G2722C. Our findings suggest that these mutations are not a marker of a particular form of Crohn's disease according to the Vienna classification. Whether the CARD153020insC and CARD15 G2722C mutations are responsible for a different etiopathogenic mechanism in a subgroup of patients remains to be studied.


Combined large cell neuroendocrine carcinoma with giant cell carcinoma of the lungs: a case report.
Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with giant cell carcinoma is extremely rare. A 65-year-old man was found to have an abnormal shadow in his left lung field. Computed tomography revealed a solid, round mass measuring 2.8 × 2.2 cm that was located in the left S9. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Histopathological examination revealed an LCNEC, combined with giant cell carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine) chemotherapy, and he has been disease-free for over 8 months. Combined LCNEC with giant cell carcinoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.


[Pathogenesis of the metabolic syndrome].
After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome.


The current state and future prospects of the fundamental research on pediatric otorhinolaryngology: an analysis of application and funding data of the National Natural Science Foundation of China from 2009 to 2019.
This study aimed to summarize the current situation and deficiencies of the fundamental research on pediatric otolaryngology-head and neck science. It is hoped that the results can provide support for the long-term development of the basic research on this subject. Information concerning the applications to and funding from the National Natural Science Foundation of China (NSFC) for otolaryngology-head and neck from 2009 to 2019 was collected and analyzed. In the past 10 years, pediatric otolaryngology-head and neck science received 150 applications, accounting for 2.92% of all applications for otolaryngology-head and neck science. Ultimately, 20 projects were funded, accounting for 2.17% of all the funded projects. There were 88 applications for children's ear science and hearing-related research, accounting for 58.67% of the applications for pediatric otolaryngology-head and neck science. Furthermore, 14 approved grants focused on cochlear implants and the genetics and mechanisms of deafness. There were 25 applications related to children's nasal science, particularly allergic rhinitis, accounting for 16.67% of the total applications. Of these, 4 applications were funded, and these mainly focused on the disease regulation and pathogenesis of allergic rhinitis. A total of 30 applications related to children's laryngopharyngeal diseases, accounting for 20% of the applications, mainly focused on obstructive sleep apnea syndrome (OSAS), adenoid hypertrophy, and tonsil hypertrophy, with only 1 application being funded. The scientific research on children's head and neck was mainly related to laryngeal papilloma and lymphatic vascular malformation, with 7 projects being applied for and 2 being funded. The fundamental research of pediatric otolaryngology-head and neck science in China is at a relatively weak level and lags behind the average level of the discipline. There are relatively few basic researchers engaged in pediatric otolaryngology-head and neck science, and the dominant research units are relatively concentrated. The basic research of children's ear science is relatively advanced in each subspecialty, so the basic research on children's unique congenital and hereditary diseases should be further strengthened.