Impact of core polarity on smectic B-induced hydrogen bond liquid crystals.
The novel series of hydrogen bond liquid crystals were synthesized from the 2-methylglutaric acid (MGA) and 4-alkyloxybenzoic acid (nOBA) compounds. The induced smectic B phase with different texture (spine texture, needle texture, mosaic texture, natural mosaic texture and marble texture) were identified by polarizing optical microscope. Due to breaking of in-plane rotational symmetry within molecular layers, smectic B phase is tempted by suppressing other usual mesophases. The mesomorphic transition temperature, enthalpy and entropy values were calculated by differential scanning calorimeter which strongly proves the existence of mesomorphism. H-bond interaction and functional groups were confirmed by the observed peak between 2910 and 2954 cm-1 in the FTIR spectra. Thermal stability and extended mesophase width (for MGA + 12OBA = 31.1) of Sm B mesophase were reported and it clearly reveals the existence of mono-phase variance in the MGA + nOBA HBLC complex. Due to the steric effect, and the increased molecular core polarity, the highly stabilized Sm B phase with different textures were observed while varying alkyloxy carbon number n = 7 to 12. Further, the origination of Sm B phase and its detailed characteristics were reported.


What do people search for in stuttering therapy: Personal goal-setting as a gold standard?
Stuttering affects people in individual ways, and there are multiple factors which may influence a person's goals when seeking therapy. Even though there is a common consensus that speech-language pathologists should discuss the individual's goals and expectations for stuttering therapy and outcomes, few studies have systematically investigated this issue. The aims of the present study were to investigate individual motivations and goal-setting related factors in stuttering therapy. The associations between self-reported impact of stuttering and the participants' perceptions of stuttering interference in communication, speaking abilities, and relationships with other people were also investigated. This study is part of a wider-ranging treatment study of individualized stuttering management tailored to the participants' personal goals and preferences. A mixed method, multiple single-case design was used to address the research questions. Twenty-one adults, age 21-61 years, took part in a pretherapy interview, which also included two quantitative measures: the Client Preferences for Stuttering Therapy-Extended version (CPST-E) and the Overall Assessment of Speakers' Experience of Stuttering-Adult version (OASES-A). Findings from the study sample was compared with a Norwegian reference group, in order to check for the representativeness of the study sample. Quantitative data showed that most participants wanted to focus on both physical and psychological aspects of therapy, and that 95% considered 'to gain a sense of control over the stuttering' as important. Participants' perspectives on their speaking ability and stuttering interference in communication were identified as central factors, particularly in social and professional settings. These outcomes aligned well with the finding of avoidance behaviors, such as avoiding words and speaking situations. Qualitative data identified four main areas that the participants wanted to improve: speech fluency, emotional functioning, activity and participation, and understanding of their stuttering. The study confirms that multiple and individual factors may influence the person's goals for therapy. Goals were mainly anchored in participants' wish of better coping in real world settings. A high degree of avoidance behavior was reported, suggesting that anxiety, and in particular linguistic-related anxiety needs to be taken into account when addressing social anxiety in fluency disorders.


Improving Ad Hoc Medical Team Performance with an Innovative "I START-END" Communication Tool.
To study the effect of a communication tool entitled: "I START-END" (I-Identify; S-Story; T-Task; A-Accomplish/Adjust; R-Resources; T-Timely Updates; E-Exit; N-Next; D-Document and Debrief) in simulated urgent scenarios in non-operating room settings (referred to as "Ad Hoc") with anesthesia residents. The "I START-END" tool was created by incorporating Crisis Resource Management (CRM) principles into a practical and user-friendly format. This was a mixed methods pre/post observational study with 47 anesthesia resident volunteers participating from July 2014 to June 2016. Each resident served as their own control, and participated in three simulated Ad Hoc scenarios. The first simulation served as a baseline. The second simulation occurred 1-2 weeks after I START-END training. The third simulation occurred 3-6 months later. Simulation performance was videotaped and reviewed by trained experts using technical skill checklists and Anesthesia Non-Technical Skills (ANTS) score. Residents filled out questionnaires, pre-simulation, 1-2 weeks after I START-END training and 3-6 months later. Concurrently, resident performance at actual Code Blue events was scored by trained observers using the Mayo High Performance Teamwork Scale. 80-90% of residents stated the tool provided an organized approach to Ad Hoc scenarios - specifically, information helpful to care of the patient was obtained more readily and better resource planning occurred as communication with the team improved. Residents stated they would continue to use the tool and apply it to other clinical settings. Resident video performance scores of technical skills showed significant improvement at the "late" session (3-6 months post exposure to the I START-END). ANTS scores were satisfactory and remained unchanged throughout. There was no difference between residents with and without I START-END training as measured by the Mayo High Performance Teamwork Scale, however, debriefing at Code Blues occurred twice as often when residents had I START-END training. Non-operating room settings are fraught with unfamiliarity that create many challenges. The I START-END tool operationalizes key CRM elements. The tool was well received by residents; it enabled them to speak up more readily, obtain vital information and continually update each other by anticipating, planning, and debriefing in an organized and collaborative way.


Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.
Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.


Microalgae's prospects in attaining sustainable economic and environmental development.
Sustainable Development Goals (SDGs) have been part of much worldwide cooperation in engineering design, nutrients production that contributes towards a better and more sustainable future. This review intends to uncover a potential renewable source that could significantly contribute to various goals under the SDGs. The prospects of algae tackling the socio-ecological, economic, and environmental issues faced globally are discussed, along with approaches of algae that can be utilized to achieve many of the SDGs are reviewed and discussed. Moreover, the recent trends in terms of engineering application that co-relate to novel algae-based technology has also been included. Apart from that, algae have high oil content which is suitable for producing affordable and clean energy, which can be used for biofuels or electricity generation. The promising characteristics of algae will lead to its global acceptance and utilization for sustainability to help create a better world.


Mitochondrial neurogastrointestinal encephalopathy in an Indian family with possible manifesting carriers of heterozygous TYMP mutation.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a distinctive autosomal recessive disorder with mitochondrial alterations due to mutations TYMP gene encoding thymidine phosphorylase. Study of clinical and biochemical characteristics of a family with MNGIE. Index case was a 32 year old man presenting with recurrent vomiting, early satiety and progressive weight loss. He had ptosis, restricted eye movements, generalized muscle wasting, and absent tendon reflexes. Lactate levels were elevated in venous blood and CSF lactate. MRI brain showed diffuse leucoencephalopathy. Barium swallow showed near total obstruction at mid portion of vertical limb of duodenum with ileus. Esophageal manometry suggested myopathy. Muscle biopsy revealed moderate numbers of ragged blue and ragged red fibers as well as cytochrome c oxidase deficient fibers. An elder brother had similar symptoms and expired after a surgical procedure and a 28 year old brother has similar illness. The father had asymptomatic bilateral ptosis with mild ophthalmoparesis. The paternal grandfather and paternal aunt also had bilateral ptosis. Clinical diagnosis of MNGIE was confirmed in the two living brothers by demonstrating severe defects of thymidine phosphorylase activity in buffy coat, elevated thymidine and deoxyuridine in plasma, and a homozygous TYMP c.893G>A mutation. This family with biochemically and genetically confirmed mitochondrial neurogastrointestinal encephalopathy syndrome uncharacteristically included heterozygous TYMP mutation carriers manifesting extra-ocular weakness. It is important to identify MNGIE patients early because therapeutic options are emerging.


Letter to the Editor: comment on 'Breast-conserving surgery with intraoperative radiotherapy in recurrent breast cancer: the patient's perspective' by Elfgen et al.
This is a comment on the article by Elfgen et al. on the use of intraoperative radiotherapy in patients with ipsilateral breast cancer recurrence following breast conserving surgery. The achievement of acceptable breast preservation rates without compromising oncologic safety in breast cancer patients is very important. Therefore, we wish to highlight a significant issue regarding axillary surgery treatment plan of their study group.


Influent carbon to phosphorus ratio drives the selection of PHA-storing organisms in a single CSTR.
Enriching a biomass with a high fraction of polyhydroxyalkanoate-storing organisms (PHA-storers) represents an essential step in the production of PHAs (bioplastics) from municipal wastewater using mixed microbial cultures. A major challenge is however to create selective growth conditions that are favourable to PHA-storers. Our study thus investigates to what extent the influent COD to phosphorus (COD:P) ratio can be used as a tool for the robust selection of PHA-storers in a single continuous-flow stirred-tank reactor (CSTR). Therefore, we operated five CSTRs in parallel, fed with synthetic wastewater (50% acetate - 50% propionate) with different COD:P ratios (200-1000 gCOD gP-1), and performed a detailed analysis of the microbial communities over long-term (30-70 solid retention times). Our study demonstrates that efficient and robust selection of PHA-storers can be achieved in a single CSTR at high influent COD:P ratios. The selective advantage for PHA-storers increases with the influent COD:P ratio, but only if growth conditions remain limited by both C-substrate and P. In contrast, selection performance deteriorates when COD:P ratios are too high and growth conditions are limited by P only. At an optimal COD:P ratio of 800 gCOD gP-1, a stable microbial community consisting of >90% PHA-storers and dominated by Pannonibacter sp. was selected in the long-term. Finally, our results suggest that high COD:P ratios provide a selective advantage to microorganisms with low cellular P requirements, explaining why different PHA-storers (i.e., Xanthobacter sp. vs. Pannonibacter sp.) were selected depending on the influent COD:P ratio (i.e., 200 vs. 800 gCOD gP-1). Overall, our results provide relevant insights for the development of a new approach for selecting PHA-storers, based on the use of a single CSTR and control of the influent COD:P ratio.


What Bariatric Surgery Can Teach Us About Endoluminal Treatment of Obesity and Metabolic Disorders.
Bariatric surgical procedures, including gastric bypass, vertical sleeve gastrectomy, and biliopancreatic diversion, are the most effective and durable treatments for obesity. In addition, These operations induce metabolic changes that provide weight-independent improvement in type 2 diabetes, fatty liver disease and other metabolic disorders. Initially thought to work by mechanical restriction of food intake or malabsorption of ingested nutrients, these procedures are now known to work through complex changes in neuroendocrine and immune signals emanating from the gut, including peptide hormones, bile acids, vagal nerve activity, and metabolites generated by the gut microbiota, all collaborating to reregulate appetite, food preference, and energy expenditure. Development of less invasive means of achieving these benefits would allow much greater dissemination of effective, gastrointestinal (GI)-targeted therapies for obesity and metabolic disorders. To reproduce the benefits of bariatric surgery, however, these endoscopic procedures and devices will need to mimic the physiological rather than the mechanical effects of these operations.


The effects of oral magnesium supplementation on glycaemic control in patients with type 2 diabetes: a systematic review and dose-response meta-analysis of controlled clinical trials.
The current systematic review and meta-analysis were conducted to evaluate the effects of oral Mg supplementation on glycaemic control in type 2 diabetes mellitus (T2DM) patients. Related articles were found by searching the PubMed, SCOPUS, Embase and Web of Science databases (from inception to 30 February 2020). A one-stage robust error meta-regression model based on inverse variance weighted least squares regression and cluster robust error variances was used for the dose-response analysis between Mg supplementation and duration of intervention and glycaemic control factors. Eighteen eligible randomised clinical trials were included in our final analysis. The dose-response testing indicated that the estimated mean difference in HbA1c at 500 mg/d was -0·73 % (95 % CI: -1·25, -0·22) suggesting modest improvement in HbA1c with strong evidence (P value: 0·004). And in fasting blood sugar (FBS) at 360 mg/d was -7·11 mg/dl (95 % CI: -14·03, -0·19) suggesting minimal amelioration in FBS with weak evidence (P value: 0·092) against the model hypothesis at this sample size. The estimated mean difference in FBS and HbA1c at 24 weeks was -15·58 mg/dl (95 % CI: -24·67, -6·49) and -0·48 (95 % CI: -0·77, -0·19), respectively, suggesting modest improvement in FBS (P value: 0·034) and HbA1c (P value: 0·001) with strong evidence against the model hypothesis at this sample size. Oral Mg supplementation could have an effect on glycaemic control in T2DM patients. However, the clinical trials so far are not sufficient to make guidelines for clinical practice.


Sex-specific parenting and depression evoked by preoptic inhibitory neurons.
The role of preoptic GABAergic inhibitory neurons was addressed in parenting, anxiety and depression. Pup exposure and forced swimming resulted in similar c-Fos activation pattern in neurons expressing vesicular GABA transporter in the preoptic area with generally stronger labeling and different distributional pattern in females than in males. Chemogenetic stimulation of preoptic GABAergic cells resulted in elevated maternal motivation and caring behavior in females and mothers but aggression toward pups in males. Behavioral effects were the opposite following inhibition of preoptic GABAergic neurons suggesting their physiological relevance. In addition, increased anxiety-like and depression-like behaviors were found following chemogenetic stimulation of the same neurons in females, whereas previous pup exposure increased only anxiety-like behavior suggesting that not the pups, but overstimulation of the cells can lead to depression-like behavior. A sexually dimorphic projection pattern of preoptic GABAergic neurons was also identified, which could mediate sex-dependent parenting and associated emotional behaviors.


Formation of reactive halide species by myeloperoxidase and eosinophil peroxidase.
The formation of chloro- and bromohydrins from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine following incubation with myeloperoxidase or eosinophil peroxidase in the presence of hydrogen peroxide, chloride and/or bromide was analysed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. These products were only formed below a certain pH threshold value, that increased with increasing halide concentration. Thermodynamic considerations on halide and pH dependencies of reduction potentials of all redox couples showed that the formation of a given reactive halide species in halide oxidation coupled with the reduction of compound I of heme peroxidases is only possible below a certain pH threshold that depends on halide concentration. The comparison of experimentally derived and calculated data revealed that Cl(2), Br(2), or BrCl will primarily be formed by the myeloperoxidase-H(2)O(2)-halide system. However, the eosinophil peroxidase-H(2)O(2)-halide system forms directly HOCl and HOBr.


Does an ED flow coordinator improve patient throughput?
At our urban academic medical center, efforts to alleviate ED overcrowding have included the implementation of a "fast track" area, increasing the ED size, using hallway beds, and ambulance diversion. In October 2012, we began the first steps of a process that created a system in which the admission process involves equal amounts of pushing and pulling to achieve the balance necessary to accomplish optimal outcomes. The foundation of the initiative was based on the use of a BSN-educated emergency nurse as a flow coordinator; a position specifically empowered to affect patient throughput in the emergency department. A determination of quality improvement was obtained by the local institutional review board for a retrospective analysis of all ED patient encounters 1 year before and 1 year after the implementation of the ED flow coordinator position. All patient encounters were included for consideration and calculation; no encounters were excluded. The flow coordinator program decreased length of stay by 87.6 minutes (P=.001) and lowered LWBS rate by 1.5% (P=.002). Monthly hospital diversion decreased from 93 hours to 43.3 hours (P=.008). Investing in a flow coordinator program can generate improvements to patient flow and can yield significant financial returns for the hospital. A decrease in diversion by an average of 49.8 hours per month translates to an annual decrease of nearly $20 million in lost potential charges. A decrease in the LWBS rate by 1.5% (31% relative decrease) per month translates to an annual decrease in lost potential charges of more than $5 million. Our research shows that an ED flow coordinator, when supported by departmental and hospital leadership, can yield significant results in a large academic medical center and that the program is able to produce an effective return on investment.


Simultaneous quantification of nine components in the plasma of depressed rats after oral administration of Chaihu-Shugan-San by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and its application to pharmacokinetic studies.
Chaihu-Shugan-San (CSS), a classic Chinese formula, has long been used to treat depression. For a better and rational use of this formula, here, we investigated the comprehensive pharmacokinetic features of multiple ingredients from CSS using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) in depressed rats. Force swimming experiments were conducted to establish a rat model of depression. Prolonged immobility time, increased plasma adrenocorticotropic hormone, and decreased plasma 5-hydroxytryptamine (5-HT) and dopamine (DA) were confirmed in this model. Nine compounds from CSS, including ferulic acid, naringin, hesperidin, meranzin hydrate, glycyrrhizic acid, saikosaponin A, nobiletin, and hesperetin, were simultaneously determined in plasma samples. Sulfamethoxazole and schisandrin were used as internal standards. The separation was performed on a C18 column with gradient elution over 10 min, and detection was executed using multiple reaction monitoring (MRM) in the positive ionization mode. The optimized MRM transitions showed no interference in rat plasma. Validation parameters were all in accordance with the current criterion. The established method was successfully applied to the pharmacokinetic study of these nine components after the oral administration of CSS to depressed rats. This study provides a chemical basis for the clinical application of this formula.


Hypergastrinemia increases proliferation of gastroduodenal epithelium during gastric ulcer healing in rats.
We investigated if hypergastrinemia exerted any influence on the proliferation of gastroduodenal epithelium during the healing of ulcers in rats. A mucosal ulcer was induced in the corpus region of the stomach in three groups of rats, which were then given vehicle, omeprazole (400 mumol/kg/day), or gastrin-17 (60 nmol/kg/day) for three or six days. A fourth group of unoperated rats served as controls. One hour before killing, [3H]thymidine was injected. The ulcer margin and corresponding control tissues were excised and processed for light microscopic determination of epithelial labeling index (LI), mitotic index, and apoptotic index. LI was also determined in other parts of the gastroduodenal mucosa. Three and six days after the ulcer operation, the LI in the vehicle-treated ulcer rats was significantly increased in the ulcer margin and in the duodenum, in comparison with the intact controls. In the ulcer margin, the mitotic index was significantly increased, in parallel with the LI; the apoptotic index remained at the control level. The LI in the ulcer margin was increased further after administration of omeprazole or gastrin-17, which elevated the plasma gastrin levels by 5-15 times. It is concluded that hypergastrinemia may increase cell proliferation in the ulcer margin, which may accelerate the rate of healing.


Visualizing the growth process of sodium microstructures in sodium batteries by in-situ 23Na MRI and NMR spectroscopy.
The growth of sodium dendrites and the associated solid electrolyte interface (SEI) layer is a critical and fundamental issue influencing the safety and cycling lifespan of sodium batteries. In this work, we use in-situ 23Na magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) techniques, along with an innovative analytical approach, to provide space-resolved and quantitative insights into the formation and evolution of sodium metal microstructures (SMSs; that is, dendritic and mossy Na metal) during the deposition and stripping processes. Our results reveal that the growing SMSs give rise to a linear increase in the overpotential until a transition voltage of 0.15 V is reached, at which point violent electrochemical decomposition of the electrolyte is triggered, leading to the formation of mossy-type SMSs and rapid battery failure. In addition, we determined the existence of NaH in the SEI on sodium metal with ex-situ NMR results. The poor electronic conductivity of NaH is beneficial for the growth of a stable SEI on sodium metal.


Cardiovascular Health Trends in Electronic Health Record Data (2012-2015): A Cross-Sectional Analysis of The Guideline Advantage™.
Electronic health record (EHR) data can measure cardiovascular health (CVH) of patient populations, but have limited generalizability when derived from one health care system. We used The Guideline Advantage™ (TGA) data repository, comprising EHR data of patients from 8 diverse health care systems, to describe CVH of adult patients and progress towards the American Heart Association's (AHA's) 2020 Impact Goals. Our analysis included 203,488 patients with 677,733 encounters recorded in TGA from 2012 to 2015. Five measures from EHRs [cigarette smoking status, body mass index (BMI), blood pressure (BP), cholesterol, and diabetes mellitus (DM)] were categorized as poor/intermediate/ideal according to AHA's Life's Simple 7 algorithm. We presented distributions and trends of CVH for each metric over time, first using all available data, and then in a subsample (n = 1,890) of patients with complete data on all metrics. Among all patients, the greatest stride towards ideal CVH attainment from 2012 to 2015 was for cigarette smoking (50.6 percent to 65 percent), followed by DM (17.3 percent to 20.7 percent) and BP (21.1 percent to 23.2 percent). Overall, prevalence of ideal CVH did not increase for any metric in the subsample. Males slightly improved in ideal CVH for BMI and cholesterol; meanwhile, females saw no improvement in ideal CVH for any metric. As ideal CVH for BP and cholesterol increased slightly among white patients, ideal CVH for BP, cholesterol, BMI, and DM worsened for non-whites. Despite improvements in some CVH metrics in the outpatient setting, more tangible progress is needed to meet AHA's 2020 Impact Goals.


Collateral input to the paraventricular and supraoptic nuclei in rat. I. Afferents from the subfornical organ and the anteroventral third ventricle region.
Injections of two fluorescent retrograde tracers were used to investigate the existence of collateral branching of input to the hypothalamic magnocellular neuroendocrine neurons. Injection of one tracer (either Fluoro-Gold or rhodamine-labeled microspheres) into the supraoptic nucleus and the other tracer into the ipsilateral paraventricular nucleus produced labeled neurons within the subfornical organ and the anteroventral third ventricle area. Some labeled cells were found to contain both fluorescent tracers (double-labeled cells), suggesting that they project to both the paraventricular and supraoptic nuclei via branching axons. Most double-labeled cells were found within the subfornical organ. Fewer of these cells were located within the nucleus medianus preopticus, and still fewer were distributed in the organum vasculosum lamina terminalis, the bed nucleus of the stria terminalis, and the medial and the lateral preoptic areas. These data present the first direct evidence that single cells may provide input to more than one magnocellular neuroendocrine nucleus. Hypothetically, hormonal release would require coordinated firing of many magnocellular cells. Thus, the branched input to these neurons may assist in the organization and the timely activation of this system in response to physiological stimuli.


The Endoscopic Endonasal Dacryocystorhinostomy (eDCR) in the Immunocompromised Patient.
We present the clinical case of a 51-year-old male patient, affected by common variable immunodeficiency (CVID). In his history recurrent orbital cellulitis, exacerbation of chronic right dacryocystitis, lacrimal sac empyema with periodic episodes of dacryocutaneous fistolization. The coexistence of these particular immunological defects and the lack of literature about similar cases required an accurate evaluation of each step of the diagnostic and therapeutic approach. We performed an endoscopic endonasal dacryocystorhinostomy with "cold" instruments. No surgical complications were observed in the immediate postsurgical period. We balanced the necessity of a follow-up based on frequent office evaluation and the current pandemic emergency, in order to not expose the patient to an additional infectious risk. The discussion will focus on several aspects: the adequacy of radiological, the "cold" surgical technique, the choice of avoiding endocanalicular prostheses. We will discuss also about the use of oral and topical therapy, avoiding probable post-surgical infectious complications.


Tumor-Infiltrating CD1a+ DCs and CD8+/FoxP3+ Ratios Served as Predictors for Clinical Outcomes in Tongue Squamous Cell Carcinoma Patients.
Tumor-infiltrating immune cells engage in an extensive crosstalk with tumors and act as two-edged swords by inhibiting or promoting cancer growth. Therefore, identifying the density and prognostic values of tumor-infiltrating immune cells will provide valuable tips for cancer treatments. In this study, we identified the density of tumor inflammatory infiltrates and the number of tumor-infiltrating immune cells, including CD3+, CD4+, CD8+, FoxP3+ T cells and CD1a+ dendritic cells (DCs) in 153 tongue squamous cell carcinomas (TSCC). High inflammatory cell infiltration was associated with better overall survival (OS) and disease free survival (DFS). Moreover, the number of CD3+, CD4+, FoxP3+ and CD1a+ cells were associated with tumor differentiation (P<0.001) and the number of FoxP3+, CD1a+ cells and CD8+/FoxP3+ ratios were also associated with tumor stage (P<0.01, P<0.01, P<0.05). In addition, patients with higher CD1a+ DCs had better OS and increased CD8+/FoxP3+ ratios were associated with improved OS and DFS (P = 0.037; P = 0.047; P = 0.033). In conclusion, our results indicated that tumor-infiltrating CD1a+ DCs and CD8+/FoxP3+ ratios were associated with favorable clinical outcomes but not independent prognostic factors for TSCC patients.


Narrative constructs in modern clinical case reporting.
Modern clinical case reporting takes the form of problem-solution narratives that redescribe symptoms in terms of disease categories. Authored almost always by those who have played a part in the medical assessment of the patient, reports historicise the salient details of an individual's illness as a complex effect of identifiable antecedent causes. Candidate hypotheses linking illness to pathological mechanisms are suggested by the patient's experience, and by data that emerge from clinical examination and investigation. Observational and interpretive statements from these considerations are fitted into a temporally inflected account of the patient's medical condition, configured from the vantage point of hindsight. Drawing on established forms of deferred telling, readers are invited to follow a story that drip-feeds a mixture of contingent and non-incidental information into the account, which engenders and frustrates curiosity, creates expectations, and challenges powers of reasoning and pattern recognition. Whereas case reporting once favoured memoir, the sentimental tale and eccentric biography as the means by which its historical narrative was cast, the preferred genres of contemporary case reporting include detective fiction, and puzzle and riddle narratives, formats that conceptualise the medical consultation in narrow problem-solution terms.


Determination of diaminopimelic acid in biological materials using high-performance liquid chromatography.
A method for the determination of diaminopimelic acid (DAPA) concentrations in feeds and rumen digesta by reversed-phase high-performance liquid chromatography using precolumn derivatization with o-phthaldialdehyde and fluorimetric detection was developed. Samples were oxidized and hydrolysed prior to analyses by HPLC. Hydrogen peroxide and formic acid were used for oxidation; hydrolyses were performed using 3 M hydrochloric acid under vacuum at 120 degrees C for 17 h. Oxidation allowed more space for DAPA-OPA peak elution and hydrochloric acid hydrolysis reduced sample clean-up and extended the column life. Hydrolysates were diluted, adjusted to pH 7 and filtered. A Beckman Model 507 autosampler with a precolumn derivatization cassette was used for the derivatization process and fluorimetric detection was used to measure the OPA derivatives. Samples were prepared in order to have on-column DAPA concentrations in the range 10-100 pmol. The relative recovery of the standard solutions added to the feed samples ranged from 98.4 to 102.8 %. The reproducibility of the method was evaluated by the analysis of eight alfalfa hay samples and eight alfalfa hay samples incubated in the rumen for 48 h and they yielded relative standard deviations of 2.04 % and 2.02%, respectively.


[The role of open surgery in the treatment of patients with a history of extended and postinfectious ureteral stricture: a case report].
The purpose of this study is to highlight the role of open surgery in the treatment of patients with a history of extended and postinfectious ureteral stricture as well as our experience with therapy. The study involved a 38-year old patient presenting at the urology service of the University Clinics of Lubumbashi with left lumbar pain, burning sensation during urination and fever. Clinical and paraclinical assessment showed extended ureteral stricture. Temporary urinary diversion (left ureterostomy) was performed followed by ureterectomy and left ureterovesical reimplantation. The postoperative course was simple. Three months after surgery the patient had no complaints, creatinine levels were normal, ultrasound and uroscan results were normal.


The Gatehouse Project: can a multilevel school intervention affect emotional wellbeing and health risk behaviours?
The aim of this study was to determine the effect of a multilevel school based intervention on adolescents' emotional wellbeing and health risk behaviours. School based cluster randomised controlled trial. Students were surveyed using laptop computers, twice in the first year of intervention and annually thereafter for a further two years. Secondary schools. 2678 year 8 students (74%) participated in the first wave of data collection. Attrition across the waves was less than 3%, 8%, and 10% respectively with no differential response rate between intervention and control groups at the subsequent waves (98% v 96%; 92% v 92%, and 90% v 89% respectively). A comparatively consistent 3% to 5% risk difference was found between intervention and control students for any drinking, any and regular smoking, and friends' alcohol and tobacco use across the three waves of follow up. The largest effect was a reduction in the reporting of regular smoking by those in the intervention group (OR 0.57, 0.62, and 0.72 at waves 2, 3, and 4 respectively). There was no significant effect of the intervention on depressive symptoms, and social and school relationships. While further research is required to determine fully the processes of change, this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours.


Is It Safe to Use a Lead Screen During Hip Arthroscopy?
To assess the radiation attenuation of lead screens in comparison to lead gowns in a simulated hip arthroscopy setting. In this quantitative laboratory study, a phantom pelvis was used to simulate the scatter produced by patients during hip arthroscopy. Radiation measurements were taken using a handheld radiation detector positioned perpendicular to the phantom pelvis at 1.5 m and 2 m. Measurements were taken without shielding as a control, behind a lead gown (0.4-mm lead equivalent), and behind a lead screen (0.5-mm lead equivalent). With the detector at 1.5 m perpendicular to the hip, equivalent radiation was attenuated by the lead screen (94%) and the lead gown (94%). With the detector at 2 m perpendicular to the hip, the lead screen at 1.7 m attenuated 95% of radiation. In hip arthroscopy, using lead screens is a safe and more comfortable alternative to wearing lead gowns. The lead screen should be at least 1.2 m from the radiation source, with the surgeon standing closely behind the screen, fully covered. Lead screens can be safely used in hip arthroscopy.


Estimating the Long-Term Epidemiological Trends and Seasonality of Hemorrhagic Fever with Renal Syndrome in China.
We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS). The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA). The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1)12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years. The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.


Detection of Mechanical Prosthetic Valve Dysfunction.
The long-term outcome of mechanical aortic and mitral prosthetic valve (A-PV, M-PV) dysfunction (PVD) remains a serious complication associated with high morbidity and mortality. We sought to evaluate the incremental diagnostic value of combined transthoracic echocardiography (TTE) and fluoroscopy (F) in patients with suspected PVD. A total of 354 patients (178 A-PV, 176 M-PV) were imaged by TTE and F within 5 days of hospital admission. PVD was confirmed by transesophageal echocardiography, computed tomography, effective thrombolysis, or surgical inspection. PVD was confirmed in 101 patients (57%) with M-PV and 99 (55%) with A-PV. Regardless of the mechanism of PVD, TTE shows good sensitivity and specificity, with accuracy of 80% for M-PV and 91% for A-PV. F shows high specificity, but low sensitivity with accuracy of 68% for M-PV and 78% for A-PV. The integration of TTE + F significantly improved accuracy both for M-PV (83%) and A-PV (96%). At ROC analysis, the combined model of TTE + F showed the highest area under the curve for the detection of PVD compared with TTE and F alone (p < 0.001). In conclusion, in patients with a clinical suspicion of PVD, the combined model of TTE + F offers incremental value over TTE or F alone. This multimodality imaging approach overcomes limitations of TTE or F alone and provides prompt identification of patients who may require further imaging assessment and/or closer follow up.


Clinical, pathological and serological features of spontaneous canine leptospirosis. An evaluation of the IgM- and IgG-specific ELISA.
The clinical, pathomorphological and serological features of acute canine leptospirosis are evaluated and the IgM- and IgG-specific ELISA for leptospirosis serology in dogs is assessed. The clinical syndrome of acute canine leptospirosis was characterized by depression, anorexia, vomiting and often haemorrhagic diarrhoea. In addition, jaundice, uraemia, elevated creatinine and alkaline phosphatase were observed in the majority of the dogs. In pups invagination of the intestines was a noteworthy finding. The clinical signs and the post-mortem findings were rather non-specific so that the clinical and post-mortem diagnosis had to be confirmed serologically. In acute clinical cases of canine leptospirosis a high anti-leptospiral IgM titre, ranging from 160 in pups to 10240 in adults, was always present, whereas the anti-leptospiral IgG titre and the agglutination titre usually were negative or low. Dogs died from leptospirosis in spite of a high anti-leptospiral IgM titre. Only two dogs having, at the first examination, a high IgM titre in conjunction with a high IgG titre survived an acute infection. The possible role of IgM and IgG in the pathogenesis of an acute leptospiral infection is discussed. Different serological patterns in reference dogs, which were not suffering from acute leptospirosis, are presented.


Role of maternal toxicity in assessing developmental toxicity in animals: a discussion.
The belief that any drug or chemical, when administered at a high enough dose, can be expected to produce fetal malformations is not consistent with the facts. However, the stress associated with maternally toxic doses can be expected to result in associated, often transient, fetal abnormalities that may not be the result of deviant organogenesis. Sometimes the toxicity toward the pregnant animal, including her embryos/fetuses since they are hardly in a sanctuary, is severe enough to result in resorption of the embryo or abortion of the fetus. Thus, it is possible that the embryolethality and other indications of developmental toxicity, produced by some drugs and chemicals, may be the result of a mechanism(s) other than selective toxicity toward the embryo. Also, some test materials have been shown to affect maternal homeostasis, thereby disrupting support to the embryo, without causing significant overt toxicity to the embryo or dam; e.g., the endocrine system of the dam is altered. Routine testing has thus far revealed a relatively limited number of true teratogens, although a large number of drugs and chemicals have resulted in fetal effects such as developmental variations when administered at doses that approach lethal levels. Such effects on the fetus should be expected when the maternal animals are stressed by the high dosages usually employed. A better understanding of the etiology and biological relevance of the embryo/fetal deviations often seen in developmental toxicology studies might help to avoid the sometimes unjustified withholding of potentially useful drugs and chemicals from the marketplace.


Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review.
This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.


Photoacousttc spectroscopy of vibrational overtones in polyatomic molecules.
Intracavity gas-phase photoacoustic spectroscopy is used to study the near IR and visible overtone spectra of propylene, 2-butene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, acetone, 2-butanone, and 3-pentanone. The spectra are described in terms of the local-mode theory of vibrations as the absorption of loosely coupled anharmonic C-H oscillators within the molecule.


Expression of Cholecystokinin and its Receptors in the Intestinal Tract of Type 2 Diabetes Patients and Healthy Controls.
Cholecystokinin (CCK) is a gut hormone originally known for its effects on gallbladder contraction and release of digestive enzymes. CCK, however, also mediates satiety and stimulate insulin secretion. Knowledge of the distribution of CCK-producing enteroendocrine cells (I cells) in humans is sparse. The general notion, based on animal data, is that I cells are present mainly in the proximal small intestine. We examined the occurrence of I cells (immunohistochemically) and the expression of CCK messenger RNA (mRNA) as well as CCK1 and CCK2 receptor mRNA along the intestines in healthy individuals and patients with type 2 diabetes. Mucosal biopsies collected with 30-cm intervals in the small intestine and from seven anatomical locations in the large intestine (using double-balloon enteroscopy) from 12 patients with type 2 diabetes and 12 gender-, age-, and body mass index-matched healthy individuals were analyzed using mRNA sequencing and immunohistochemical staining. We observed a gradual decrease in CCK mRNA expression and density of CCK-immunoreactive cells from duodenum to ileum. Very few CCK-immunoreactive cells and nearly undetectable CCK mRNA expression were found in the large intestine. No significant differences were seen between the groups. Expression of CCK receptors was observed in the duodenum of both groups. Both density of CCK cells and expression of CCK mRNA decreased through the small intestine in both groups with low levels in the large intestine. Patients with type 2 diabetes did not have altered density of CCK cells or expression of CCK mRNA in intestinal mucosa.


Identification of beta-hemolytic streptococci isolated from hospitalized children in Baghdad.
Two hundred and twenty four hospitalized children in Baghdad aged between 1 month and 10 years were examined for Streptococcal infections. Thirty-four percent of the throat and saliva specimens were positive for beta-hemolytic streptococci. Males were more susceptible to infection with group A streptococci than females. Streptococcus of group A was isolated from 39.5% of the positive cases while group G was 47.4%. The etiological significance of the latter group in tonsillitis and otitis media is to be further investigated. Ninety six percent of the isolated streptococci were T typable and 13.3% of the strains were M typable. A high frequency of type T-11 was found in streptococcal infections. T type 3875 was found to be a new provisional type. All isolates were M untypable, and antiopacity factor negative except for two isolates of T type 4 which were positive in both typings.


Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: a case-control study.
To evaluate clinicopathological factors and survival outcome of patients with advanced epithelial ovarian carcinoma undergoing multiple bowel resections to achieve optimal (< or = 1 cm) cytoreduction. A case-control study was performed identifying patients undergoing optimal primary cytoreductive surgery with > or = 2 bowel resections between 10/1997 and 2/2006. The two control groups consisted of (1) patients undergoing optimal cytoreduction with < or = 1 bowel resections matched [1:2] for age and stage and (2) patients left with suboptimal disease. Cox proportional hazards model were used to evaluate the effects of demographic and surgico-pathologic factors on survival outcome. A total of 34 patients underwent > or = 2 bowel resections. Sixty-eight patients underwent < or = 1 bowel resections. All patients had optimal cytoreduction and 40/102 patients (39.2%) underwent complete cytoreduction. Patients undergoing multiple bowel resections experienced a higher EBL (700 v 500 mL, p=0.01) and longer LOS (10 v 7 days, p=0.01) compared to patients with < or = 1 bowel resections. Multivariate analysis revealed the amount of residual disease to be a statistically significant and radiation therapy to the right pelvic sidewall and cul-de-sac independent predictor of overall survival. The median overall survival time for patients undergoing > or = 2 bowel resections was 28.3 months, which was comparable to patients undergoing < or = 1 bowel resections, (37.8 months, p=0.09) but statistically significantly superior to patients left with suboptimal residual disease (12 months, p=0.02). Although primary surgery that includes > or = 2 bowel resections is associated with longer LOS and a higher EBL, such extensive procedures are warranted if they will contribute to an overall optimal residual disease state.


Cystic Fibrosis Modulator Therapies.
Cystic fibrosis (CF) is an inherited multisystemic disease that can cause progressive bronchiectasis, pancreatic endocrine and exocrine insufficiency, distal intestinal obstruction syndrome, liver dysfunction, and other disorders. Traditional therapies focused on the treatment or prevention of damage to each organ system with incremental modalities such as nebulized medications for the lungs, insulin for diabetes, and supplementation with pancreatic enzymes. However, the advent of highly effective modulator therapies that target specific cystic fibrosis transmembrane conductance regulator protein malformations resulting from individual genetic mutations has transformed the lives and prognosis for persons with CF.


Improved treatment results for childhood acute myeloid leukemia in Taiwan.
To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.


Piribedil in Parkinson's syndrome: a clinical study.
The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functions of activity of daily living (ADL), and appeared to have a preferential effect on parkinsonian tremor. However, treatment was difficult to control primarily because of severe psychiatric side effects.


Treating the metabolic syndrome using angiotensin receptor antagonists that selectively modulate peroxisome proliferator-activated receptor-gamma.
The metabolic syndrome, defined as a cluster of visceral obesity, insulin resistance, dyslipidemia and elevated blood pressure, is associated with pro-thrombotic, pro-atherogenic and inflammatory risk factors that predispose to cardiovascular disease. Although activators of the peroxisome proliferator-activated receptors (PPARalpha,gamma,delta) in various combinations are under development for treating the metabolic syndrome, they are hampered by adverse effects related to increased adipogenesis, weight gain, fluid overload and carcinogenesis. The recent discovery that telmisartan and irbesartan, antihypertensive angiotensin II type 1 receptor (AT1-R) blockers (ARBs), were uniquely capable of activating PPARgamma, has provided a novel approach to addressing the multifactorial components of the metabolic syndrome. Both drugs have established favorable safety profiles and can activate PPARgamma at concentrations potentially achievable at therapeutic doses. Emerging studies have revealed that both these drugs have beneficial metabolic profiles. This information provides a strategic rationale and pharmacological platform for the development of novel dual ARB/PPARgamma agonists to target the metabolic syndrome and its cardiovascular sequelae, for which therapy is presently insufficient or non-existent. Beneficial effects of these agents include increased energy expenditure, improved lipid profile, increased insulin sensitivity, blood pressure reduction, and amelioration of the associated pro-inflammatory and pro-atherogenic risk profiles. The potential benefit for treatment of the metabolic syndrome, cardiovascular protection, and prevention of related end-organ complications could be of immense clinical value.


Partial purification and properties of N-acetylhistamine deacetylase.
The enzyme catalyzing the deacetylaction of N-acetylhistamine was partially purified about 160-fold from rat liver extract and its properties were investigated. The purification procedure included DEAE-cellulose chromatography, precipitation with ammonium sulfate and DEAE-cellulose rechromatography. The enzyme contains a labile -SH group that is essential for its activity. Mn2+ and Co2+ enhanced the deacetylation reaction at low concentration. The molecular weight of the deacetylase was estimated to be about 70 000 from gel-filtration. Among various acetyl derivatives tested so far, N-acetylhistamine and to a lesser extent N-acetyltyramine served as the substrates. The Km value was 0.3 mM at the optimum pH 8.0 for N-acetylhistamine. Diphenhysramine, an antihistaminergic agent, inhibited the deacetylation remarkably.


Neuroendocrine aspects of pineal tumors.
The evaluation and treatment of pineal region tumors has changed dramatically in the past decade. New imaging techniques result in earlier diagnosis. Surgical techniques now permit removal of benign tumors (about one third of cases). Pathologic diagnosis is obtained for the remainder, and postoperative therapy can be planned rationally. Germ cell tumors pose a particularly difficult problem for the pathologist because they often contain mixed germ cell elements. Biologic markers, beta HCG and AFP, aid diagnosis and can be monitored in serum and CSF to assess response to treatment. Only boys develop precocious puberty with pineal tumors. What appears to be puberty is actually pseudoprecocious puberty, due to ectopic production of HCG by their neoplasms (choriocarcinomas or germinomas with syncytiotrophoblastic giant cells). HCG can stimulate tests to produce testosterone, but FSH is necessary (together with LH or HCG) to stimulate ovaries to produce estrogen. Diabetes insipidus with pineal tumors is usually due to spread to the hypothalamus by ventricular seeding, but we report a case of aqueductal stenosis with diabetes insipidus resulting from a massively dilated third ventricle. Rarely, hydrocephalus may trigger true precocious puberty, a syndrome easily differentiated from pseudoprecocious puberty by endocrinologic tests. There are no biologic markers to diagnose pineal parenchymal tumors. Elevation of melatonin in plasma or CSF and increased tumor biosynthetic activity has been reported in isolated cases, but the range of melatonin values in normals is very wide, and melatonin levels do not correlate with specific pathologic tumor types. Both parenchymal and nonparenchymal tumors may increase melatonin nonspecifically by interfering with regulatory mechanisms of the normal pineal gland.


An Air-Rechargeable Zn Battery Enabled by Organic-Inorganic Hybrid Cathode.
Self-charging power systems collecting energy harvesting technology and batteries are attracting extensive attention. To solve the disadvantages of the traditional integrated system, such as highly dependent on energy supply and complex structure, an air-rechargeable Zn battery based on MoS2/PANI cathode is reported. Benefited from the excellent conductivity desolvation shield of PANI, the MoS2/PANI cathode exhibits ultra-high capacity (304.98 mAh g-1 in N2 and 351.25 mAh g-1 in air). In particular, this battery has the ability to collect, convert and store energy simultaneously by an air-rechargeable process of the spontaneous redox reaction between the discharged cathode and O2 from air. The air-rechargeable Zn batteries display a high open-circuit voltage (1.15 V), an unforgettable discharge capacity (316.09 mAh g-1 and the air-rechargeable depth is 89.99%) and good air-recharging stability (291.22 mAh g-1 after 50 air recharging/galvanostatic current discharge cycle). Most importantly, both our quasi-solid zinc ion batteries and batteries modules have excellent performance and practicability. This work will provide a promising research direction for the material design and device assembly of the next-generation self-powered system.


Early development of NADPH diaphorase-expressing neurons in the brain of the urodele amphibian Pleurodeles waltl.
The distribution of nitrergic cells was studied in the brain of the urodele amphibian Pleurodeles waltl during embryonic and larval stages by means of NADPH-diaphorase histochemistry. The first positive neurons were observed at embryonic stage 30 in the ventrolateral area of the caudal rhombencephalon. Subsequently (stage 33b), weakly reactive cells appeared in the isthmic tegmentum, the mesencephalic tegmentum, the hypothalamus, and the nucleus of the solitary tract. At initial larval stages (34-38), two new groups of NADPH-diaphorase-positive cells appeared in the caudal telencephalon (the amygdaloid region) and in the middle reticular nucleus. During the beginning of the active larval life (stages 39-42), reactive cells were found in the granule cell layer of the olfactory bulb and in the telencephalic pallium. As in the adult, the nitrergic cells in the central nervous system are widely distributed during early development, pointing to important roles of nitric oxide through ontogenesis. The sequence of appearance of nitrergic cells suggests an early involvement in reticulospinal control most likely related to locomotor behavior.


Mini drug pump for ophthalmic use.
To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use. Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the bench-top and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 x 7.7 x 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma aqueous drainage device. To determine the ability to refill and also the patency of the cannula, at intervals of 4-6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 microL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed by slit lamp examination, photography, and fluorescein angiography. Bench-top testing showed 2.0 microL/min delivery when using 0.4 mW of power for electrolysis. One-way valves showed reliable opening pressures of 470 mmHg. All implanted devices refilled at 4-6 weeks intervals for 4-6 months. No infection was seen. No devices extruded. No filtering bleb formed over the implant. A prototype ocular mini drug pump was built, implanted, and refilled. Such a platform needs more testing to determine the long term biocompatibility of an electrically-controlled implanted pump. Testing with various pharmacological agents is needed to determine its ultimate potential for ophthalmic use.


The Effects of Concurrent Training Combined with Low-Carbohydrate High-Fat Ketogenic Diet on Body Composition and Aerobic Performance: A Systematic Review and Meta-Analysis.
(1) Background: Recently, studies have emerged to explore the effects of concurrent training (CT) with a low-carb, high-fat ketogenic diet (LCHF) on body composition and aerobic performance and observed its benefits. However, a large variance in the study design and observations is presented, which needs to be comprehensively assessed. We here thus completed a systematic review and meta-analysis to characterize the effects of the intervention combining CT and LCHF on body composition and aerobic capacity in people with training experience as compared to that combining CT and other dietary strategies. (2) Methods: A search strategy based on the PICOS principle was used to find literature in the databases of PubMed, Web of Science, EBSCO, Sport-discuss, and Medline. The quality and risk of bias in the studies were independently assessed by two researchers. (3) Result: Eight studies consisting of 170 participants were included in this work. The pooled results showed no significant effects of CT with LCHF on lean mass (SMD = -0.08, 95% CI -0.44 to 0.3, p = 0.69), body fat percentage (SMD = -0.29, 95% CI -0.66 to 0.08, p = 0.13), body mass (SMD = -0.21, 95% CI -0.53 to 0.11, p = 0.2), VO2max (SMD = -0.01, 95% CI -0.4 to 0.37, p = 0.95), and time (or distance) to complete the aerobic tests (SMD = -0.02, 95% CI -0.41 to 0.37, p = 0.1). Subgroup analyses also showed that the training background of participants (i.e., recreationally trained participants or professionally trained participants) and intervention duration (e.g., > or ≤six weeks) did not significantly affect the results. (4) Conclusions: This systematic review and meta-analysis provide evidence that compared to other dietary strategies, using LCHF with CT cannot induce greater benefits for lean mass, body fat percentage, body mass, VO2max, and aerobic performance in trained participants.


P-wave locking in the postventricular atrial refractory period of cardiac resynchronization devices. Management with the Biotronik system.
Electrical desynchronization in cardiac resynchronization therapy (CRT) occurs when sinus P waves are continually locked in the postventricular atrial refractory period (PVARP). This process is characterized by sequences of a P wave as an atrial event in the PVARP followed by a conducted and sensed ventricular event. Such sequences are more common in patients with a prolonged PR interval, often initiated by premature ventricular complexes (PVC) and terminated by PVCs or slowing of the sinus rate. Specific algorithms automatically identify a recurring pattern of P wave locking in the PVARP, whereupon they shorten the PVARP temporarily until atrial tracking is restored with the programmed sensed AV interval. The Biotronik family of Lumax CRT devices use an AV control window which is not an algorithm that "unlocks" P waves trapped in the PVARP. Rather, it prevents P waves from becoming trapped in the PVARP. A ventricular sensed event occurring within the AV control interval does not start a PVARP so that P wave locking cannot occur when the AV conduction time is shorter than the AV control interval.


Strategies for improving the efficacy of bioengineered bone constructs: a perspective.
Bioengineered bone scaffolds are intended for use in large bone defects. Successful bone constructs should stimulate and support both the onset and the continuance of bone ingrowth. In an attempt to improve their performance and to compete with the one of autologous bone grafts, a growing symbiosis at the biological and material level is required. Recent advances have been made to further exploit the osteogenic potential of MSCs in scaffold development. Current research encompasses new strategies for reducing cell death after implantation and the manufacturing of tailored, instructive scaffolds.


Long-range skin Josephson supercurrent across a van der Waals ferromagnet.
The emerging field of superconducting spintronics promises new quantum device architectures without energy dissipation. When entering a ferromagnet, a supercurrent commonly behaves as a spin singlet that decays rapidly; in contrast, a spin-triplet supercurrent can transport over much longer distances, and is therefore more desirable, but so far has been observed much less frequently. Here, by using the van der Waals ferromagnet Fe3GeTe2 (F) and spin-singlet superconductor NbSe2 (S), we construct lateral Josephson junctions of S/F/S with accurate interface control to realize long-range skin supercurrent. The observed supercurrent across the ferromagnet can extend over 300 nm, and exhibits distinct quantum interference patterns in an external magnetic field. Strikingly, the supercurrent displays pronounced skin characteristics, with its density peaked at the surfaces or edges of the ferromagnet. Our central findings shed new light on the convergence of superconductivity and spintronics based on two-dimensional materials.


Effects of donor-specific antibodies on engraftment and long-term survival after allogeneic hematopoietic stem cell transplantation-A systematic review and meta-analysis.
The presence of donor-specific antibodies (DSAs) have been reported to be associated with an increased risk of primary graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its effects on the time to engraftment and long-term outcomes remain unclear. We performed a systematic review and meta-analysis of studies investigating the impact of DSAs on engraftment and long-term survival of patients undergoing allo-HSCT. We systematically searched PubMed, Embase, the Cochrane Library, and CBM. Data were analyzed using RevMan5.4. Pooled hazard ratio (HR), standard mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) are calculated for time-to-event data, continuous data, discontinuous data respectively. 17 eligible studies were included, involving 2169 patients main receiving haploidentical SCT (haplo-SCT) or umbilical cord blood transplantation (UCBT). Meta-analysis showed that DSAs-positive patients are associated with significantly higher risk of GF(OR = 12.87, 95%CI, 6.45-25.70; P < 0.00001; OR = 4.76, 95%CI, 2.88-7.87), poorer neutrophil engraftment (HR = 2.20, 95%CI, 1.02-4.73; P = 0.04; HR = 1.83, 95%CI, 1.46-2.30; P < 0.00001), worse OS (HR = 3.19, 95%CI, 1.85-5.50; P < 0.0001; HR = 1.68, 95%CI, 1.04-2.71; P = 0.03), and inferior PFS (HR = 4.25, 95%CI, 1.59-11.40; P = 0.004; HR = 4.83, 95%CI, 1.65-14.12; P = 0.004) in haplo-SCT and UCBT, respectively.


Calcium mobilization in C5a-stimulated adult and newborn bovine neutrophils.
Calcium (Ca2+) is an important second messenger central to many neutrophil (PMN) functional activities. Impaired Ca2+ mobilization in newborn PMNs following membrane perturbation could be one of the mechanisms underlying observed abnormalities in neonatal PMN function. To compare Ca2+ mobilization in bovine newborn and adult PMNs, cytosolic Ca2+ responses after stimulation with recombinant human C5a (rHC5a) were measured. PMNs from normal newborn calves (N = 6) and adult cows (N = 5) were loaded with fura-2/AM for 60 min at room temperature and the fluorescence changes monitored following stimulation with 0.1, 1, 10, or 50 nM rHC5a in Ca2(+)-containing buffer. Resting levels of Ca2+ in both newborn (54.6 +/- 1.9 nM) and adult (57.3 +/- 1.8 nM) bovine PMNs were comparable. After stimulation with rHC5a, a rapid rise of cytosolic Ca2+ was observed, which peaked within 20 sec and was followed by a sustained phase of elevated Ca2+ lasting up to 20 min. There were no significant differences (P greater than 0.05) in peak levels of cytosolic Ca2+ obtained by newborn and adult PMNs at 0.1, 10, and 50 nM rHC5a. At 1 nM rHC5a, newborn PMNs reached significantly (P less than 0.05) higher levels of cytosolic Ca2+ (217.9 +/- 21.7 nM) than did adult PMNs (158.7 +/- 7.9 nM). At 1 nM rHC5a, newborn PMNs also sustained higher levels of cytosolic Ca2+ for 3 min following the peak. At all concentrations of rHC5a tested, the time required to reach the peak and the duration of the peak were comparable in both populations. In the absence of extracellular Ca2+ (Ca2(+)-free buffer with 1 mM EGTA), resting levels of cytosolic Ca2+ were lower in both newborn (33.3 +/- 2.9 nM) and adult PMNs (27.9 +/- 2.4 nM) and the magnitude of the peak response to rHC5a was diminished at all concentrations of agonist. Additionally, in the absence of extracellular Ca2+, the return to basal cytosolic Ca2+ levels occurred rapidly and the sustained phase of increased cytosolic Ca2+ seen with rHC5a-stimulated PMNs in Ca2(+)-containing buffer was virtually eliminated. These results indicate that bovine PMNs respond well to rHC5a, that stimulated newborn bovine PMNs can mobilize Ca2+ as efficiently as adult PMNs, and that the sustained cytosolic Ca2+ response to rHC5a in both age groups requires both release of Ca2+ from intracellular stores as well as influx of extracellular Ca2+. Such data suggest that observed functional deficits in newborn bovine PMNs are probably not related to improper mobilization of Ca2+ following stimulation.


Ferroptosis landscape in prostate cancer from molecular and metabolic perspective.
Prostate cancer is a major disease that threatens men's health. Its rapid progression, easy metastasis, and late castration resistance have brought obstacles to treatment. It is necessary to find new effective anticancer methods. Ferroptosis is a novel iron-dependent programmed cell death that plays a role in various cancers. Understanding how ferroptosis is regulated in prostate cancer will help us to use it as a new way to kill cancer cells. In this review, we summarize the regulation and role of ferroptosis in prostate cancer and the relationship with AR from the perspective of metabolism and molecular pathways. We also discuss the feasibility of ferroptosis in prostate cancer treatment and describe current limitations and prospects, providing a reference for future research and clinical application of ferroptosis.


Humanized bone marrow mouse model as a preclinical tool to assess therapy-mediated hematotoxicity.
Preclinical in vivo studies can help guide the selection of agents and regimens for clinical testing. However, one of the challenges in screening anticancer therapies is the assessment of off-target human toxicity. There is a need for in vivo models that can simulate efficacy and toxicities of promising therapeutic regimens. For example, hematopoietic cells of human origin are particularly sensitive to a variety of chemotherapeutic regimens, but in vivo models to assess potential toxicities have not been developed. In this study, a xenograft model containing humanized bone marrow is utilized as an in vivo assay to monitor hematotoxicity. A proof-of-concept, temozolomide-based regimen was developed that inhibits tumor xenograft growth. This regimen was selected for testing because it has been previously shown to cause myelosuppression in mice and humans. The dose-intensive regimen was administered to NOD.Cg-Prkdc(scid)IL2rg(tm1Wjl)/Sz (NOD/SCID/γchain(null)), reconstituted with human hematopoietic cells, and the impact of treatment on human hematopoiesis was evaluated. The dose-intensive regimen resulted in significant decreases in growth of human glioblastoma xenografts. When this regimen was administered to mice containing humanized bone marrow, flow cytometric analyses indicated that the human bone marrow cells were significantly more sensitive to treatment than the murine bone marrow cells and that the regimen was highly toxic to human-derived hematopoietic cells of all lineages (progenitor, lymphoid, and myeloid). The humanized bone marrow xenograft model described has the potential to be used as a platform for monitoring the impact of anticancer therapies on human hematopoiesis and could lead to subsequent refinement of therapies prior to clinical evaluation.


Estimation of cancer risk due to radiation exposure for some daily consumption of foods.
Considering the increasing concern about the cancer risk caused by environmental radiological effects related to the food consumption, the study was carried out evaluate the activity concentrations and cancer risk assessments of 226 Ra,232 Th, and 40 K in 72 food samples collected from different suppliers in Tehran Province of Iran. The specific activity concentration was determined by means of a high-resolution high-purity germanium gamma-spectroscopy system. The collected various sample groups were wheat, rice, meat, milk, and mushroom. The maximum concentration of 226 Ra and 232 Th was found in the wheat sample, equal to 0.7862 Bq/kg and 0.968 Bq/kg, respectively, whereas for 40 K, it was 598.35 Bq/kg in the milk sample. The annual effective dose rate ranged from 2.47 μSv/y in mushroom to 64.66 μSv/y in rice. The average excess lifetime cancer risk (ELCR) was varied from 1.60 × 10-5 for mushroom to 4.20 × 10-4 for milk, with the total ELCR value from main daily diets 1.37 × 10-3, which was a little more than the acceptable ELCR limit of 10-3. The ELCR due to five main daily diets was a little more than the acceptable ELCR limit of 10-3 for radiological risk in general.


[Early congenital syphilis (7 cases observed in Bangui Hospital Central African Empire) (author's transl)].
In an infant of good condition, skin changes, anemia, hepato-splenomegalia and more over radiological osseous changes are symptoms of great value which are to be confirmed by a serological test of the baby and its mother. Treatment is very effective but it would be better to protect the foetus by an early detection and treatment of the syphilitic pregnant woman.


Eimeria maxima: a comparison of two laboratory strains with a fresh isolate.
Oocysts of the Weybridge and Houghton strains of Eimeria maxima and a fresh field isolate were similar and measured on average 30-9 X 22-4 mum. The Weybridge strain and the field isolate produced similar pathogenic effects in 6-week-old chickens, high doses causing 50-80% mortality and severe weight loss. The Houghton strain was slightly less pathogenic and few birds died but more oocysts were produced. With each strain, a single dose gave complete immunity to a light challenge with the homologous strain. Two or 3 immunizing doses gave complete immunity to a heavy homologous challenge but were not sufficient to protect against heterologous challenge.


Leiomyosarcoma in a premenopausal patient after uterine artery embolization.
A premenopausal 45-year-old woman underwent uterine artery embolization for suspected symptomatic leiomyomata. Fourteen months later, with renewed symptoms and a new pelvic mass, metastatic leiomyosarcoma was diagnosed. A lack of clinical response to a technically successful embolization should alert care providers that further evaluation and/or therapy is needed.


Fatal infantile lactic acidosis and a novel homozygous mutation in the SUCLG1 gene: a mitochondrial DNA depletion disorder.
Mitochondrial DNA (mtDNA) depletion syndromes are autosomal recessive conditions in which the mtDNA copy number is greatly decreased in affected tissues. The encephalomyopathic group of these syndromes comprise mutations in SUCLA2 and SUCLG1 subunits [1]. In this report, we describe a patient with fatal infantile lactic acidosis associated with mutations in the SUCLG1 gene and mtDNA depletion. Histological and enzymatic abnormalities in skeletal muscle support the diagnosis of this recently described mitochondrial disorder. This case is unique in that prenatal imaging suggested the diagnosis and that the confirmatory molecular diagnosis was established at 2 weeks of age. We describe prenatal MRI and neonatal laboratory disturbances that can point the clinician toward consideration of this diagnosis when treating infantile lactic acidosis.


Immunoscintigraphy and radioimmunotherapy in patients with pancreatic carcinoma.
A new monoclonal antibody (BW 494/32) labeled with 131I or 111In was used for planar and tomographic immunoscintigraphy (IS) in patients with pancreatic carcinoma. It appears that IS for pancreatic carcinoma and its metastases remains a hopeful but still difficult procedure and labeling with 111In is of advantage and results in more convincing images in the case of tumor lesions distant from liver and spleen. Attempts at radioimmunotherapy with 131I-anti-CA 19-9 and with 131I-494/32 in a patient with local recurrence of a pancreatic cancer and with large liver metastases were without success because of extremely poor blood supply to the metastatic tumor masses. Intraarterial infusion of the tracer without or with blockade and perfusion of the common hepatic artery with saline solution could not enhance the tracer uptake compared to that after intravenous infusion. High intratumoral concentrations, however, as achieved e.g. by intratumoral instillation in animal studies, represent a necessary precondition for effective beta-irradiation of tumor lesions.


Comparative kinetics of the sulphatases A.
The kinetic behaviour of the sulphatase A from kangaroo liver is that of a simple hysteretic system involving a substrate-modified form of the enzyme. The equilibrium between the native and substrate-modified forms is influenced by one of the reaction products, sulphate. The behaviour of the system differs markedly from that involving the ox enzyme and a generalised model is presented to account for the behaviour of the sulphatases A from ox, human, rat and kangaroo livers.


Glucose infusion suppresses acute restraint stress-induced peripheral and central sympathetic responses in rats.
Acute restraint stress (RS) induces sympathetic activation such as elevating plasma catecholamines, resulting in increase in blood glucose. We aimed to investigate whether glucose infusion affects the RS-induced sympathetic responses. Plasma catecholamines were measured by high-performance liquid chromatography with electrochemical detection. Blood glucose levels were measured with a glucometer and a glucose assay kit. Cardiac parameters were measured by echocardiographic and hemodynamic analysis. Prostanoid levels in the paraventricular nucleus of hypothalamus (PVN) microdialysates were measured by liquid chromatography-ion trap tandem mass spectrometry analysis. RS significantly increased plasma noradrenaline and adrenaline. Intravenous infusion of a 5% glucose solution significantly attenuated the RS-induced elevation of plasma adrenaline but did not alter the plasma noradrenaline. Glucose administration during RS suppressed the progression of cardiac impairment by attenuating the decline rates in left ventricular diastolic, end-diastolic volume, stroke volume, fractional shortening, and ejection fraction. Both Intravenous and intracerebroventricular infusion of glucose solution significantly attenuated the RS-induced elevation of thromboxane B2 (TxB2) (a metabolite of TxA2) levels in the PVN but did not alter prostaglandin E2 levels in the PVN. Our results demonstrate that glucose infusion suppresses RS-induced elevation of plasma adrenaline and left ventricular dysfunction. In the brain, glucose infusion suppresses RS-induced production of TxA2 in the PVN.


Abnormal fetal heart rate tracings in patients with thick meconium staining of the amniotic fluid: Xu et al.
The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Xu H, Calvet M, Wei S-Q, Luo Z-C, Fraser WD. Abnormal fetal heart rate tracing patterns in patients with thick meconium staining of the amniotic fluid: association with perinatal outcomes. Am J Obstet Gynecol 2009;200:283.e1-283.e7. The full discussion appears at www.AJOG.org, pages e1-e4.


[Diagnostic value of electromyography in revealing the laterality of the motor deficit in brain tumors].
Electromyographic studies of anterior tibial muscles supplemented by simultaneous induction of Babinski's reflex indicated the appearance of bioelectrical activity in the extremities contralateral to the tumour which suggested the generalization of tone alterations and helped determine the laterization of the pathological process even when there were no clinical manifestations of motor deficit. Having analyzed their own and literature data, the authors came to the conclusion that the contralateral response observed on the electromyogram in the form of prolonged bioelectrical activity with simultaneous appearance of tonic tension in the crus flexors in the absence of clinically evident motor deficit is explained by the presence of the crossover protective reflex on the spinal level.


Enhancement of reference memory in aged rats by specific activation of 5-HT(4) receptors using an olfactory associative discrimination task.
In normal aging, or pathological brain diseases in humans, implicit memory (or procedural memory in rats) is spared while explicit memory (or reference memory in rats) is deeply impaired. Selective activation of 5-HT(4) receptors by a partial 5-HT(4) receptor agonist (SL65.0155) improved memory performance in an olfactory associative discrimination task in aged rats. Detailed analysis of subcategories of long-term memory using a hippocampal-dependent olfactory associative discrimination task revealed a substantial benefit on reference memory. This agent could be used to treat early mnesic deficits observed in normal aging or in neurodegenerative disorders like Alzheimer disease.


The ability of foods to stain two composite resins.
In this bench study, coffee and soy sauce stained composite resin restorations to a significantly greater degree than did tea or cola beverage. Generally, the greatest degree of staining with all samples occurred during the first week of the study time. The stain penetration was superficial and was estimated to be 5 mu or less.


Comparisons of Quality of Life and Functional and Oncological Outcomes after Orthotopic Neobladder Reconstruction: Prostate-Sparing Cystectomy versus Conventional Radical Cystoprostatectomy.
To compare health-related quality of life and oncological and functional outcomes on erectile function, continence, and voiding function among bladder patients who underwent orthotopic neobladder reconstruction after prostate-sparing cystectomy (PSC) and conventional radical cystoprostatectomy (CRC). This is a retrospective cohort study from a single surgeon. During 2007 to 2015, we identified 25 of 186 male patients receiving radical cystectomies due to bladder cancer who underwent orthotopic neobladder reconstruction, 14 patients with PSC and the other 11 patients with CRC. International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30-item questionnaire (EORTC-QLQ-C30), and self-catheterizations were used to evaluate functional outcomes in the baseline and 1 year after operation. There were better physical and social functioning scales, less fatigue symptoms, better IIEF (16 versus 3.7, p = 0.01), and less self-catheterization rate (33% versus 89% p = 0.006) in the PSC group. The oncologic outcomes were the same between two groups. For selected patients with bladder cancer who underwent neobladder reconstruction, prostate-sparing cystectomy provided better sexuality preservation, less daily self-catheterization, and better physical function and social function scales without compromising overall survival.


[Pediatric endocrinological service in the Russian Federation: current state and development prospects].
The article provides brief data on the prevalence of endocrine diseases in children in the Russian Federation, provides the main normative documents regulating the provision of medical care in the field of «pediatric endocrinology», data on the state of the bed fund (children's endocrinological beds), the number of specialized children's departments in the Russian Federation, the number of children's endocrinologists.


Positron emission tomography in cerebrovascular disorders.
The introduction of positron emission tomography (PET) as a powerful imaging modality has played a major role in the understanding of the pathophysiological bases for cerebrovascular disorders. PET is the only technique that allows measurement of regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen and glucose metabolism with detail and accuracy. Using PET, these physiological parameters can be measured to determine the extent of the disease from the early stages of cerebrovascular disorders to acute cerebral infarction. Significant hemodynamic and metabolic abnormalities are noted in chronic ischemia, but no structural changes are noted on anatomic images. PET studies have shown that in many patients in the early phases (10 to 12 hours) of clinically diagnosed acute stroke, a substantial area of ischemia exists, which, if untreated, will become irreversibly damaged. Similar to the results achieved in patients with acute myocardial infarction, appropriate intervention in patients with cerebrovascular disorders may significantly reduce the extent of injury to the brain. PET also has been useful in predicting functional recovery and monitoring the effects of various therapeutic approaches. Although functional imaging of the brain with single photon emission computed tomography can successfully be used in the investigation of several disorders of the brain, its role in cerebrovascular disorders is quite limited. PET is a unique modality that studies ischemic diseases of the brain, and it potentially could play a significant role in the management of patients with cerebrovascular disease. This will be further realized when aggressive approaches are used routinely in the future.


The haemostatic system components of neointima forming in polyester aortic grafts in the early postoperative period.
The aim of the studies was to determine the content of certain components of the haemostatic system in the neointima of a polyester graft implanted in the dog abdominal aorta over a 7-day period of observation. The neointima of an aortic polyester graft in the early postoperative period possesses a high thromboplastic activity, greater than that of the artery or vein, and containing prothrombin, active thrombin, platelet aggregating substances and heparin neutralizing substances. The plasminogen activator activity in the neointima of the polyester graft is also considerably higher than in the intima of arteries and veins.


S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.
The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-L-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine. Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-L-methionine tosylate over a 6-week trial. Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-L-methionine. Gastrointestinal symptoms and headaches were the most common side effects. Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-L-methionine warrants a placebo-controlled trial in resistant depression.


Outcome in patients with an ICD incorporating cardiac resynchronisation therapy: differences between primary and secondary prophylaxis.
The incidence of ventricular tachyarrhythmias in ICD patients with cardiac resynchronisation therapy (CRT-D) is not well studied. To analyse event free survival in CRT-D patients with a primary or a secondary prophylactic ICD indication. Prospective, single centre. Eighty-six patients, 44% with a primary prophylactic indication. Actuarial event-free rates for mortality and arrhythmias were calculated. Baseline clinical characteristics were not significantly different between primary and secondary prophylaxis. Primary prophylaxis patients were more likely to be in NYHA class III. Over 21 months, 724 ventricular events with therapy occurred in 36 patients (42%). The actuarial event-free rates, at 1 and 3 years, from appropriate ICD therapy were higher (P<0.001) for primary (79.0% and 67.8%) than for secondary prophylaxis (45.6% and 27.0%). Appropriate ICD therapy occurred more in NYHA class II compared to class III (P=0.016). Underlying disease (ischemic versus non-ischemic) and functional class did not play a role in multivariate analysis. Important arrhythmic events in patients with heart failure, and CRT-D occur at a very high rate when the indication is secondary prophylaxis. Patients with primary prophylaxis have an annual event rate of 10%, even though they tend to have a worse heart failure class.


Efficacy of prolonged interferon-alpha treatment in chronic hepatitis B patients with HBeAb: comparison between 6 and 12 months of therapy.
We compared the response and the relapse rates of HBeAb-positive patients treated with interferon-alpha for 6 or 12 months. Thirty-eight HBeAb-positive patients which chronic hepatitis B were randomly allocated into two groups: Group I (19 patients receiving 10 MU of recombinant interferon-alpha 2b three times a week for 2 months, followed by 5 MU three times a week for 2 months and then 3 MU three times a week for 2 months); Group II (19 patients receiving 10 MU of recombinant interferon-alpha 2b three times a week for 2 months, followed by 5 MU three times a week for 2 months and then 3 MU three times a week for 8 months). At the end of treatment, alanine aminotransferase normalization was higher but not more significant in Group I than in II (53% vs 26%), while hepatitis B virus DNA clearance was similar in both groups (21% in Group I vs 26% in Group II). However, at 12 months of follow-up, biochemical relapses occurred only in Group I (60% vs 0% in Groups I and II, respectively). Five complete responders cleared hepatitis B surface antigen at that time. In conclusion, prolonged treatment of HBeAb patients is efficient in reducing the biochemical relapse.


Tumor embolism in the right atrium after hepatic artery ligation for hepatoma.
A case of tumor embolism in the right atrium after hepatic artery ligation for hepatoma was reported. Patient was a 55 year old male complaining of upper abdominal pain. Preoperative angiogram and scintigram revealed multinodular hepatomas in the right and middle his condition gradually deteriorated thereafter and sudden hypotension occurred on the 22nd postoperative day with a fatal sequela. At autopsy, the orifice of the right atrium was impacted by a tumor embolus. The cause of death seemed to be attributable to this embolus liberated from the hepatic veins. Accordingly, we emphasize the necessity of careful angiographic evaluation not only of the hepatic inflow but of the outflow tract in performing hepatic artery ligation as a treatment of nonresectable hepatoma.


Have health inequities, the COVID-19 pandemic and climate change led to the deadliest heatwave in France since 2003?
Between 2015 and 2019, 5700 excess deaths were observed during heatwaves in France. The summer of 2020 combined exceptionally high temperatures with the COVID-19 pandemic. The associated health impacts of this unique situation are described in this study. This is an observational study based on indicators of the French heat prevention plan. Mortality and morbidity data during heatwaves were compared between 2020 and previous years, alongside COVID-19 in-hospital mortality. In total, 1921 additional deaths (+18.2%) were observed during the 2020 heatwaves, which is the largest number of deaths observed since 2003. Less than 100 deaths were attributed to COVID-19 during the heatwaves of 2020. Exceptionally high temperatures driven by climate change, combined with health inequities exacerbated by the COVID-19 outbreak, may have increased vulnerability to heat in 2020.


Causation mechanisms in car-to-vulnerable road user crashes: implications for active safety systems.
Vulnerable road users (VRUs), such as pedestrians and bicyclists, are often involved in crashes with passenger cars. One way to prevent these crashes is to deploy active safety systems that support the car drivers and/or VRUs. However, to develop such systems, a thorough understanding of crash causation mechanisms is required. The aim of this study is to identify crash causation mechanisms from the perspective of the VRUs, and to explore the implications of these mechanisms for the development of active safety systems. Data originate from the European project SafetyNet, where 995 crashes were in-depth investigated using the SafetyNet Accident Causation System (SNACS). To limit the scope, this study analyzed only intersection crashes involving VRUs. A total of 56 VRU crashes were aggregated. Results suggest that, while 30% of the VRUs did not see the conflict car due to visual obstructions in the traffic environment, 70% of the VRUs saw the car before the collision, but still misunderstood the traffic situation and/or made an inadequate plan of action. An important implication that follows from this is that, while detection of cars is clearly an issue that needs to be addressed, it is even more important to help the VRUs to correctly understand traffic situation (e.g., does the driver intend to slow down, and if s/he does, is it to let the VRU cross or for some other reason?). The former issue suggests a role for various cooperative active safety systems, as the obstacles are generally impenetrable with regular sensors. The latter issue is less straightforward. While various systems can be proposed, such as providing gap size estimation and reducing the car speed variability, the functional merits of each such a system need to be further investigated.


Metabolism of 1,4-dinitro-2-methylpyrrole, a mutagen formed by a sorbic acid-nitrite reaction, by intestinal bacteria.
1,4-Dinitro-2-methylpyrrole (DNMP), a mutagenic product formed by the interaction of two common food additives, sorbic acid and sodium nitrite, was transformed to 1-nitro-2-methyl-4-aminopyrrole (NMAP) by human fecal mixtures and various intestinal bacterial strains. Under anaerobic conditions the cell suspensions of Actinomyces, Bacteroides, Clostridium, Eubacterium, Fusobacterium, and Peptostreptococcus spp. demonstrated the nitroreduction activity. Under aerobic conditions, only Actinomyces and Bacteroides spp. showed activity, and this was at a decreased level. In cell suspensions of Bacteroides thetaiotaomicron VPI 5482, NAD(P)H and glucose accelerated the reduction rate, whereas dicoumarol and heat significantly inhibited the rate, and flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) did not affect the rate. With cell-free preparations of the same strain, reduction required NAD(P)H as a cofactor in a dose-dependent fashion and was inactivated by air and heat.


Correlation of Cerebral Microbleed Distribution to Amyloid Burden in Patients with Primary Intracerebral Hemorrhage.
The underlying pathology of cerebral microbleeds (CMBs) with mixed lobar and deep distribution remains contentious. The aim of this study was to correlate CMBs distribution to β-amyloid burden in patients with primary intracerebral hemorrhage (ICH). Fourty-seven ICH patients underwent magnetic resonance susceptibility-weighted imaging and 11C-Pittsburgh Compound B positron emission tomography. The amyloid burden was expressed as standardized uptake value ratio with reference to cerebellum, and presented as median (interquartile range). Patients were categorized into the lobar, mixed (both lobar and deep regions), and deep types of CMB. Comparing the lobar (17%), mixed (59.6%) and deep (23.4%) CMB types, the global amyloid burden was significantly higher in the mixed type than the deep type (1.10 [1.03-1.25] vs 1.00 [0.97-1.09], p = 0.011), but lower than in the lobar type (1.48 [1.18-1.50], p = 0.048). On multivariable analysis, the ratio of lobar to deep CMB number was positively correlated with global (p = 0.028) and occipital (p = 0.031) amyloid burden. In primary ICH, patients with lobar and mixed CMB types are associated with increased amyloid burden than patients with deep type. The ratio of lobar to deep CMB number is an independent indicator of cerebral β-amyloid deposition.