One-pot molten salt method for constructing CdS/C3N4 nanojunctions with highly enhanced photocatalytic performance for hydrogen evolution reaction.
The construction of heterojunction photocatalysts for efficiently utilizing solar energy has attracted considerable attention to solve the energy crisis and reduce environmental pollution. In this study, we use the energy released from an easily-occurred exothermic chemical reaction to serve as the drive force to trigger the formation of CdS and C3N4 nanocomposites which are successfully fabricated with cadmium nitrate and thiourea without addition of any solvents and protection of inert gas at initial temperature, a little higher than the melting point of thiourea. The as-prepared CdS/C3N4 materials exhibit high efficiency for photocatalytic hydrogen evolution reaction (HER) with the HER rate as high as 15,866 μmol/(g∙hr) under visible light irradiation (λ > 420 nm), which is 89 and 9 times those of pristine C3N4 and CdS, respectively. Also, the apparent quantum efficiency (AQE) of CdS/C3N4-1:2-200-2 (CdS/C3N4-1:2-200-2 means the ratio of Cd to S is 1:2 and the reaction temperature is set at 200°C for two hours) reaches 3.25% at λ = 420 ± 15 nm. After irradiated for more than 24 hr, the HER efficiencies of CdS/C3N4 do not exhibit any attenuation. The DFT calculation suggests that the charge difference causes an internal electric field from C3N4 pointing to CdS, which can more effectively promote the transfer of photogenerated electrons from CdS to C3N4. Therefore, most HER should occur on C3N4 surface where photogenerated electrons accumulate, which largely protects CdS from photo-corrosion.


Erratum: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.
[This corrects the article DOI: 10.1093/ofid/ofv040.].


A new method for characterization of low grade gliomas using ultra low field magnetic resonance imaging.
Low grade gliomas were studied with ultra low field magnetic resonance imaging (ULF MRI). The tumors exhibited high tissue contrast in both T1 and T2-weighted images as compared to normal brain tissue. Moreover they were sharply delineated towards the surrounding brain tissue. When compared with X-ray computed tomography the tumors were more readily detected and delineated by using ultra-low field magnetic imaging. A computer-assisted classification procedure was used to define new regions of interest for relaxation time estimations. By using this procedure more accurate estimations of the T1 and T2 values were obtained.


[The diagnosis of pancreatic carcinoma by combined endoscopic retrograde pancreatiography, aspiration cytology and carcinoembryonic antigen determination in the pancreatic secretion (author's transl)].
The reliability of diagnostic procedures in pancreatic disease can be significantly increased by the combination of endoscopic retrograde pancreaticography, determination of carcinoembryonic antigen and cytological examination of the aspirated pancreatic section. In the present study all cases of pancreatic carcinoma were correctly diagnosed by these methods. These combined diagnostic procedures seem to provide the basis for potential progress in the diagnosis of pancreatic carcinoma.


Association of SCNN1A Single Nucleotide Polymorphisms with neonatal respiratory distress syndrome.
Increasing evidence has demonstrated that lung fluid absorption disorders might be an important cause of neonatal respiratory distress syndrome (RDS) by influencing gas exchange or surfactant function. The SCNN1A gene, which encodes the α-ENaC, might predispose infants to RDS. To explore whether the single-nucleotide polymorphisms (SNPs) of SCNN1A are associated with RDS, we conducted a case-control study to investigate the RDS-associated loci in Han Chinese infants. Seven target SNPs were selected from the SCNN1A gene and were genotyped using the improved multiplex ligase detection reaction (iMLDR). In the total sample, only rs4149570 was associated with NRDS; this association was further confirmed in logistic regression analysis after adjusting for birth weight, gestational age and sex. In the subgroup of infants whose gestational age was 37 weeks and older, in addition to rs4149570, rs7956915 also showed a significant association with RDS. Interestingly, these associations were only observed in term infants. No significant association was observed between the target SNPs and the risk of RDS in preterm infants. We report for the first time that the rs4149570 and rs7956915 polymorphisms of SCNN1A might play important roles in the susceptibility to RDS, particularly in term infants.


Interindividual comparability of blood glucose alterations after meals of complex carbohydrates.
Young male and female probands underwent an DGTT (oral glucose tolerance test) using a glucose load of 1 g/kg b.wt. The alterations in blood glucose levels were checked and plotted by a Biostator. A week later groups of those probands were fed an isocaloric meal of complex CH, namely either potatoes, noodles or white bread. The resulting BG curves were also checked by a Biostator. It turned out that: 1. the shapes of the BG curves after glucose load were not interindividually comparable. 2. there was neither a similarity of the shapes of the BG curves within the groups after any of the different CH levels. 3. But if one compares the shape of the BG curves after glucose load and after a meal of any of the complex CH of one and the same person, there is a striking similarity in those curve shapes. The differences between them lie just in the mostly lower BG values of the curves after CH meals compared with those after glucose load. 4. Therefore the resulting graph of both of those curves is in all observed cases a straight line with a probability better than 0.001, called OGTT-calibrating resulting graph.


Anti-inflammatory Effect of a Limonin Derivative In Vivo and Its Mechanisms in RAW264.7 Cells.
A potential new limonoid derivative, (12S,12aS)-6,6,8a,12a-tetramethyl-12-(5-(4-(piperidin-1-yl)butanoyl)furan-3-yl)decahydro-1H,3H-oxireno[2,3-d]pyrano[4',3':3,3a]isobenzofuro[5,4-f]isochromene-3,8,10(6H,9aH)-trione (I-C-1), has been screened for its anti-inflammatory activity. This study aimed to demonstrate the anti-inflammatory activities of I-C-1 and to further explore the underlying mechanisms of these activities in RAW264.7 macrophages. We verified the anti-inflammatory activity of I-C-1 in vivo by a carrageenan-induced paw edema model in rats and cotton pellet-induced granuloma in mice. Further, we found that I-C-1 significantly inhibited levels of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-induced RAW264.7 cells. I-C-1 demonstrated strong inhibition of the NF-κB activation through repression of the IKKα and IKKβ phosphorylations, as well as a significant suppression of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, an upstream of the NF-κB pathway. Additionally, we verified the inhibitory effect of I-C-1 on PI3K phosphorylation by immunofluorescence assay and compared the effects of I-C-1 with the PI3K inhibitor LY294002 in IL-1β, IL-6, and TNF-α levels. The data indicated that I-C-1 likely acts as an inhibitor of PI3K, exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-κB signaling pathway. Based on these findings, we believe that I-C-1 has the potential to be further developed as a potential therapeutic agent for inflammatory-related diseases.


Tumor microenvironment components: Allies of cancer progression.
Cancer is a disease that affects millions of individuals worldwide and has a great impact on public health. Therefore, the study of tumor biology and an understanding of how the components of the tumor microenvironment behave and interact is extremely important for cancer research. Factors expressed by the components of the tumor microenvironment and induce angiogenesis have important roles in the onset and progression of the tumor. These components are represented by the extracellular matrix, fibroblasts, adipocytes, immune cells, and macrophages, besides endothelial cells, which modulate tumor cells and the tumor microenvironment to favor survival and the progression of cancer. The characteristics and function of the main stromal components and their mechanisms of interaction with the tumor cells that contribute to progression, tumor invasion, and tumor spread will be addressed in this review. Furthermore, reviewing these components is expected to indicate their importance as possible prognostic markers and therapeutic targets.


The effect of storage of blood on mononuclear cell antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.
Antibody-dependent cellular cytotoxicity (ADCC) activity to herpes simplex virus-infected cells of fresh mononuclear cells was compared with the ADCC activity of mononuclear cells obtained from blood after 1, 2, and 18 hr of storage at room temperature. After 1 and 2 hr of blood storage, mononuclear cell ADCC activity decrease significantly (P less than 0.05 and P less than 0.01, respectively) and was undetectable after 18 hr of storage. The use of preservative-free heparin and various effector to target cell ratios further verified these results. There was no significant difference between natural killer cytotoxicity of mononuclear cells obtained from fresh blood compared with that obtained from blood after 1 and 2 hr of storage. These data demonstrate the importance of rapid assay of clinical specimens utilized to determine differences in ADCC activity of patient populations.


Does the devil facial tumour produce immunosuppressive cytokines as an immune evasion strategy?
A unique transmissible cancer known as the Devil Facial Tumour Disease (DFTD) is threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. This disease is highly unusual as it is one of only two naturally occurring contagious cancers. The tumour is transmitted by biting and is able to spread between genetically diverse hosts. Why the tumours are not recognised as foreign and rejected by the host immune system in unknown. One mechanism that allows human cancers to avoid immune suppression is by producing cytokines which down-regulate the hosts immune system. Four key cytokines involved in this process are TGFβ1, VEGF-A, IL-10 and IL-6. In this study we investigated whether these cytokines could be involved in immune avoidance in DFTD. To do this we compared expression of these cytokines in tumour and control tissues using qPCR. We found no significant upregulation of any of these cytokines in tumour tissue. We therefore conclude that these cytokines do not play a role in the spread of DFTD. Further work will be needed to elucidate how DFTD cells avoid immune rejection.


Lineage specificity of the evolutionary dynamics of the mtDNA D-loop region in rodents.
This paper reports an intraorder study on the D-loop-containing region of the mitochondrial DNA in rodents. A complete multialignment of this region is not feasible with the exception of some conserved regions. The comparative analysis of 25 complete rodent sequences from 23 species plus one lagomorph has revealed that only the central domain (CD), a conserved region of about 80 bp in the extended termination-associated sequences (ETAS) domain, adjacent to the CD, the ETAS1, and conserved sequence block (CSB) 1 blocks are present in all rodent species, whereas the presence of CSB2 and CSB3 is erratic within the order. We have also found a conserved region of 90 bp located between tRNAPro and ETAS1 present in fat dormouse, squirrel, guinea pig, and rabbit. Repeated sequences are present in both the ETAS and the CSB domain, but the repeats differ in length, copy number, and base composition in different species. The potential use of the D-loop for evolutionary studies has been investigated; the presence/absence of conserved blocks and/or repeated sequences cannot be used as a reliable phylogenetic marker, since in some cases they may be shared by distantly related organisms but not by close ones, while in other ones a relationship between tree topology and presence/absence of such motifs is observed. Better results can be obtained by the use of the CD, which, however, due to its reduced size, when used for tracing a phylogenetic tree, shows some nodes with low statistical support.


Organic solvent tolerance of Escherichia coli is independent of OmpF levels in the membrane.
The organic solvent tolerance of Escherichia coli was measured under conditions in which OmpF levels were controlled by various means as follows: alteration of NaCl concentration in the medium, transformation with a stress-responsive gene (marA, robA, or soxS), or disruption of the ompF gene. It was shown that solvent tolerance of E. coli did not depend upon OmpF levels in the membrane.


Maternal use of hormonal contraception and risk of childhood leukaemia: a nationwide, population-based cohort study.
Maternal hormonal contraception has been suspected of being linked to an increased risk of childhood cancer. The aim of this study was to assess the association between maternal use of hormonal contraception and diagnosis of leukaemia in their children. In this cohort study, we followed a nationwide cohort of 1 185 157 liveborn children between 1996 and 2014 listed in the Danish Medical Birth Registry and identified those diagnosed with leukaemia in the Danish Cancer Registry. Redeemed prescriptions from the Danish National Prescription Registry provided information about maternal hormonal contraceptive use, categorised as: no use (never used contraception before birth; reference category), previous use (>3 months before start of pregnancy), and recent use (≤3 months before and during pregnancy). We also calculated risk estimates separately for maternal hormonal contraceptive use during pregnancy. The primary outcome of interest was a diagnosis of any leukaemia in the children. Secondary outcomes were diagnoses of lymphoid leukaemia and non-lymphoid leukaemia. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for risk of leukaemia in children. The Data Protection Agency registration number for this study is 2017-41-5221. Between Jan 1, 1996, and Dec 31, 2014, the 1 185 157 liveborn children accumulated 11 114 290 person-years of follow-up (median 9·3 years, IQR 4·6-14·2), during which 606 children were diagnosed with leukaemia (465 with lymphoid leukaemia and 141 with non-lymphoid leukaemia). Children born to women with recent use of any type of hormonal contraception were at higher risk for any leukaemia than children of women who never used contraception (HR 1·46, 95% CI 1·09-1·96; p=0·011); and for exposure during pregancy the risk was 1·78 (0·95-3·31; p=0·070). No association was found between timing of use and risk for lymphoid leukaemia (HR 1·23, 95% CI 0·97-1·57, p=0·089, for previous use and 1·27, 0·90-1·80, p=0·167, for recent use); however, the HRs for non-lymphoid leukaemia were 2·17 (1·22-3·87; p=0·008) for recent use and 3·87 (1·48-10·15; p=0·006) for use during pregnancy. Hormonal contraception use close to or during pregnancy might have resulted in one additional case of leukaemia per about 50 000 exposed children, or 25 cases during the 9-year study period. Our findings suggest the maternal hormonal use affects non-lymphoid leukaemia development in children. Since almost no risk factors have been established for childhood leukaemia, these findings suggest an important direction for future research into its causes and prevention. The Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation.


Analysis of polysorbate and its polyoxyethylated metabolite.
Polysorbates are used as emulsifiers in a number of pharmaceuticals and have been implicated as the possible toxic agent in the neonatal vitamin supplement, E-Ferol. In the investigation of the toxicity of this compound, it was necessary to find a method to separate and quantitate polysorbate and its polyoxyethylated metabolite from biological fluids. A high-performance liquid chromatography method was developed which combines the use of a 500 A mu Styragel size exclusion column with an ammonium cobaltothiocyanate complexation column and detection at 620 or 320 nm. The detection limit is approximately 5 micrograms. The method was used to demonstrate that polysorbate was metabolized in vitro by hepatocytes and that the urinary metabolite in humans is comparable to that produced by the rat.


Community Health Needs Assessment Data and Community Recovery From COVID-19.
The COVID-19 pandemic has had a significant impact beyond physical morbidity and mortality. A mid-cycle Community Health Needs Assessment survey was administered in 1 community to generate data to evaluate change in community well-being since the beginning of the pandemic. Surveys were mailed to 2,000 randomly selected residents in Olmsetd County, Minnesota. The surveys included the WHO Well-being Index (previously included in the 2018 Community Health Needs Assessment) and new subjective questions regarding behavior change. Changes in well-being were calculated using a propensity-matched cohort, and behavior change was reported as proportions of the whole. Data analysis was completed in 2021. Total survey respondents were 569 people in 2018 and 723 people in 2021. Well-being scores from the WHO Well-being Index showed a statistically significant decrease (score reduction of -8.44) from 2018 to 2021. All the 5 questions from the WHO Well-being Index also had an individual significant decrease; with the question regarding interest in life showing the greatest decrease. Individuals reported decreased subjective physical and mental well-being and increased substance use (alcohol, marijuana, and tobacco). Households also reported decreased household incomes and worse household finances since the start of the pandemic. Using the Community Health Needs Assessment infrastructure, 1 community was able to compare prepandemic with postpandemic data, which showed decreased well-being and increased substance use and financial stress. Other public health planners can similarly conduct interval surveys on the basis of their Community Health Needs Assessment questionnaires to tailor ongoing Community Health Improvement Plan programming to postpandemic needs and track community mental health and well-being recovery.


Anti-osteoporosis effects of Anemarrhenae Rhizoma / Phellodendri Chinensis Cortex herb pair and its major active components in diabetic rats and zebrafish.
Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been widely used in traditional Chinese medicines for the treatment of diabetic osteoporosis. However, the anti-diabetic osteoporotic active components of AR/PCC remain unclear. This study aimed to explore the major active ingredients in AR/PCC for its protective effects against bone deterioration induced by diabetes. The aqueous extracts of AR/PCC with different proportions (AR:PCC = 1:3, 1:2, 1:1, 2:1 and 3:1, w/w) were prepared. Streptozotocin-induced diabetic rats were orally administrated with the AR/PCC extracts. The absorbed phytochemical compounds in serum of diabetic rats were identified by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method and their contents in the AR/PCC extracts were determined by high performance liquid chromatography-ultraviolet detector-evaporative light scattering detector method. The absorbed compounds in the extracts were considered as the major potential active components in AR/PCC, and their combination was defined as M-AR/PCC. A component-knockout approach was applied to evaluate the contribution of each compound in M-AR/PCC. The larvae and adults of diabetic zebrafish models were then used to evaluated the anti-diabetic osteoporotic performance of the M-AR/PCC. The real-time reverse transcription polymerase chain reaction technique was applied to study the regulation effects of M-AR/PCC on osteogenesis and osteoclastgensis in diabetic zebrafish models. The phenotypes of diabetic osteoporosis rats induced by streptozotocin were reversed by the oral administration of AR/PCC extracts with different ratios, as evidenced by the increased bone mineral density, bone volume density, trabecular thickness, trabecular number, and decreased trabecular separation of femoral metaphysis. Seven phytochemical compounds were detected in the serum and their contents in AR/PCC varied dramatically with different proportions, including 1 xanthone glycoside and 6 alkaloids. By using diabetic zebrafish larvae model and compound-knockout strategy, each compound in M-AR/PCC were proved to play an indispensable role in the positive regulatory actions in the bone mass of diabetic zebrafish. Furthermore, the herb pair with a ratio of 1:1 and the related M-AR/PCC showed the best therapeutic effects on diabetic osteoporosis. They showed similar performances on the inhibition of the tartrate-resistant acid phosphatase activity and the promotion of the alkaline phosphatase activity in diabetic adult zebrafish model. The M-AR/PCC treatment could decrease the blood glucose, upregulate the mRNA expression levels of osteoblast-related genes (alp, runx2b and opg) and downregulate the expression of osteoclast-related genes (acp5α, rankl and sost) in streptozotocin-induced zebrafish. AR/PCC herb pair and its major active components possess potent anti-diabetic osteoporotic effect on streptozotocin-induced in vivo models. The combination of the seven active compounds derived from AR/PCC herbal pair could be a potential agent for protection against osteoporosis associated with diabetes.


The right to refuse treatment and blood transfusion.
A Hungarian bioethicist looks at the Hungarian law on the refusal of treatment, and of blood transfusion by Jehovah's Witnesses.


Aggressive treatment of severe diffuse peritonitis: a prospective study.
In a prospective study of 22 patients with diffuse peritonitis managed by the method of electively staged multiple laparotomies, the abdomen was left open in 9 patients. The patients were selected on the basis of the severity of their intra-abdominal infection: only massive faecal peritonitis, postoperative peritonitis and pancreatic abscesses were included. These amounted to only 9 per cent of all patients with intra-abdominal infection treated over a 2-year period. Up to seven re-operations were required per patient. In view of a high mortality rate of 32 per cent, the superiority of this aggressive management strategy over conventional methods is not fully established.


Neurobiology of Circadian Rhythm Regulation.
In this review, we provide a summary of the field of mammalian circadian neurobiology circa 2015. While many additional details have emerged in the intervening 7 years, understanding of the fundamental structure and function of this critical neural system remains intact. Thus, the present review continues to provide a valuable introduction for those seeking an integrative multilevel overview of the circadian system. In brief, the circadian system comprises a coupled network of molecular/cellular- and tissue-level oscillators, hierarchically coordinated by the hypothalamic suprachiasmatic nuclear circadian pacemaker, and entrained by both photic and nonphotic signals.


Long-term follow-up of children with magnetic resonance imaging and ultrasound after treatment of brain tumors.
This paper compares the results of MRI and US follow-up examinations of 46 children who had undergone surgery for brain tumors. The cases included 42 posterior fossa tumors, 3 supratentorial tumors and 1 upper cervical spinal cord tumor. US examination proved to be less specific and sensitive than MRI. However, when a "bone window" is available, US is, because of the ease of its application, better suited for frequent routine examinations. Long-term follow-up should, therefore, consist of frequent regular US examinations combined with yearly MRI examinations.


Twelve-month discontinuation of etonogestrel implant in an outpatient pediatric setting.
The etonogestrel (ENG) contraceptive implant is the most effective reversible contraceptive method. Uptake remains limited in adolescents, a population at high risk for unintended pregnancy. The objectives of this study were to determine the 12-month discontinuation rate of the ENG implant among adolescents in an outpatient setting and to characterize risk factors for discontinuation. A retrospective chart review identified adolescent females aged 12 to 22years who received the ENG implant in one pediatric institution between January 1, 2011, and April 15, 2014. Patients were categorized into ENG discontinuers (removed prior to 12months) and ENG continuers (continued for ≥12months). Associations between demographic, clinical and postplacement characteristics with ENG discontinuation category were assessed with t tests, χ(2)/Fisher's Exact Tests and backwards stepwise logistic regression. Of the 750 patients who had an ENG implant inserted, 77 (10.3%) had the device removed prior to 12months of use. The mean length of implant use for those who discontinued was 7.5months. Problematic bleeding was the most commonly cited reason for discontinuation. Older age at time of insertion, history of pregnancy and ≥1 medical visit for implant concerns (not including removal) were independently predictive (p<.01) of method discontinuation. The vast majority of adolescents continued the ENG implant at 12months, making it an excellent contraceptive choice for adolescents within the outpatient pediatric setting. Greater efforts should be made to increase its use by pediatric providers. The ENG implant is an excellent contraceptive option for adolescents in the outpatient pediatric setting.


XPC initiation codon mutation in xeroderma pigmentosum patients with and without neurological symptoms.
Two unrelated xeroderma pigmentosum (XP) patients, with and without neurological abnormalities, respectively, had identical defects in the XPC DNA nucleotide excision repair (NER) gene. Patient XP21BE, a 27-year-old woman, had developmental delay and early onset of sensorineural hearing loss. In contrast, patient XP329BE, a 13-year-old boy, had a normal neurological examination. Both patients had marked lentiginous hyperpigmentation and multiple skin cancers at an early age. Their cultured fibroblasts showed similar hypersensitivity to killing by UV and reduced repair of DNA photoproducts. Cells from both patients had a homozygous c.2T>G mutation in the XPC gene which changed the ATG initiation codon to arginine (AGG). Both had low levels of XPC message and no detectable XPC protein on Western blotting. There was no functional XPC activity in both as revealed by the failure of localization of XPC and other NER proteins at the sites of UV-induced DNA damage in a sensitive in vivo immunofluorescence assay. XPC cDNA containing the initiation codon mutation was functionally inactive in a post-UV host cell reactivation (HCR) assay. Microsatellite markers flanking the XPC gene showed only a small region of identity ( approximately 30kBP), indicating that the patients were not closely related. Thus, the initiation codon mutation resulted in DNA repair deficiency in cells from both patients and greatly increased cancer susceptibility. The neurological abnormalities in patient XP21BE may be related to close consanguinity and simultaneous inheritance of other recessive genes or other gene modifying effects rather than the influence of XPC gene itself.


Virtual reality uterine resectoscopic simulator: face and construct validation and comparative evaluation in an educational environment.
Recognizing that resectoscopic simulation may have an educational role, this pilot study was designed to evaluate the face validity and educational utility of a virtual reality uterine resectoscope training system. A pilot prospective comparative study of novice and expert hysteroscopists' performance on a targeting exercise and myomectomy with the virtual loop electrode. At baseline, expert and novice resectoscopists each performed both exercises. Following instruction, novices practiced each exercise a total of 9 times with the 10th recorded as the training outcome. Results were compared both to baseline and to those of the experts. Data were analyzed with the paired t and Wilcoxon rank sum tests as appropriate. At baseline, all experts touched 4 targets in a mean of 33 seconds with no perforations, compared to a mean of 2 for the 11 novices in a mean of 57 seconds (P=0.0034) with one perforation. In 3 minutes, the experts removed a mean of 97.3% of the virtual myoma, compared to 66.1% for the novices (P=0.0153). On the 10th "run," novices touched a mean of 4 targets in a mean of 23 seconds, an improvement from baseline (P=0.0004) and improved to 89% on the myoma resection exercise (P=0.0515) 36.3% over baseline. Although this pilot study has a relatively small sample size and represents the results at one institution, it demonstrates that virtual reality resectoscopic systems have the potential to measure and improve the technical skills of novices before they operate on human patients.


Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.
Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.


Anorectal carcinoma after infliximab therapy in Crohn's disease: report of a case.
Infliximab, monoclonal antibody against tumor necrosis factor alpha, is an effective agent in the therapy of Crohn's disease. Although therapy with infliximab is generally well tolerated, there is an obvious concern about the effect of this treatment on the incidence of cancer. We report a case of mucinous anorectal adenocarcinoma observed in a 39-year-old patient with long-standing Crohn's disease after therapy with two courses of infliximab. The carcinoma was discovered fortuitously after abdominoperineal resection. Despite clear margins, the tumor recurred in a few months and progressed during combination chemotherapy. Although there is currently no definitive proof of a causal link between infliximab therapy and cancer, the present observation and other reports in the literature should lead to a careful evaluation of the possibility of increased cancer risk in patients treated with this new agent.


Allogeneic mesenchymal stem cells for treatment of severe burn injury.
The most important determinant of survival post-burn injury is wound healing. For decades, allogeneic mesenchymal stem cells (MSCs) have been suggested as a potential treatment for severe burn injuries. This report describes a patient with a severe burn injury whose wounds did not heal with over 18 months of conventional burn care. When treated with allogeneic MSCs, wound healing accelerated with no adverse treatment complications. Wound sites showed no evidence of keloids or hypertrophic formation during a 6-year follow-up period. This therapeutic use of allogeneic MSCs for large non-healing burn wounds was deemed safe and effective and has great treatment potential.


A novel selenium nanoparticles-enhanced chemiluminescence system for determination of dinitrobutylphenol.
A novel selenium nanoparticles (Se NPs)-amplified chemiluminescence (CL) reaction, Se NPs-potassium permanganate-dinitrobutylphenol (DNBP), for the determination of DNBP at gram per milliliter level is described. In the present study, it was found that direct reaction of DNBP with potassium permanganate (KMnO4) in the acidic mediums elicited light emission, which was greatly enhanced by selenium nanoparticles. Under optimum conditions, the CL intensity is linearly related to the concentration of DNBP in the range of 1.0×10(-7)-8.0×10(-5)g mL(-1) with a detection limit (3σ) of 3.1×10(-8) g mL(-1). The relative standard deviation for 11 determinations of 2.5×10(-5) gm L(-1) DNBP is 2.07%. The Se NPs were prepared by the chemical hydrothermal method. It was found that catalytic properties of Se NPs were higher than those of microparticles (MPs). In addition, scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to characterize the Se NPs. Appropriate sensitivity, selectivity and precision were among notable features of the proposed method. The method was successfully applied to the determination of DNBP in the water samples of different origins. Moreover, the possible mechanism for the new CL reaction was also discussed.


Lentivirally transduced dendritic cells as a tool for cancer immunotherapy.
Dendritic cells (DC) are the professional antigen-presenting cells of the immune system, fully equipped to prime naive T cells and thus essential components for cancer immunotherapy. We tested the influence of several elements (cPPT, trip, WPRE, SIN) on the transduction efficiency of human DC. Human and murine DC were transduced with tNGFR-encoding lentiviruses to assess the effect of transduction on phenotype and function. Human DC were transduced with lentiviruses encoding huIi80MAGE-A3 and murine DC with huIi80tOVA to test antigen presentation. A self-inactivating (SIN) lentiviral vector containing the trip element was most efficient in transducing human DC. The transduction of DC with trip/SIN tNGFR encoding lentiviral vectors at MOI 15 resulted in stable gene expression in up to 94.6% (murine) and 88.2% (human) of the mature DC, without perturbing viability, phenotype and function. Human huIi80MAGE-A3-transduced DC were able to stimulate MAGE-A3-specific CD4(+) and CD8(+) T cell clones and could prime both MAGE-A3-specific CD4(+) and CD8(+) T cells in vitro. Murine huIi80tOVA-transduced DC were able to present OVA peptides in the context of MHC class I and class II in vitro and induced a strong OVA-specific cytotoxic T lymphocyte response in vivo, that was protective against subsequent challenge with OVA-expressing tumor cells. We show that, using lentiviral vectors, efficient gene transfer in human and murine DC can be obtained and that these DC can elicit antigen-specific immune responses in vitro and in vivo. The composition of the transfer vector has a major impact on the transduction efficiency.


Somatic, behavioral, and reproductive disturbances in mice following neonatal administration of sodium L-aspartate.
Sodium L-aspartate (ASP) was administered to neonatal mice according to an increasing dose schedule from Days 2--11 after birth. Adult ASP-treated animals showed large increases in body weight over controls along with stunted body length. The ASP group also showed decreases in locomotor and exploratory behavior. Reproductive dysfunction occurred in both female and male ASP-treated animals. Among treated animals, females had fewer pregnancies and smaller litters while males showed reduced fertility. Evidence of multiple endocrine dysfunction in ASP-treated animals was reflected by decreased pituitary, thyroid, ovaries and tested weights, along with delayed onset of puberty in females. These results demonstrate that sodium L-aspartate produces a syndrome similar to that seen following the administration of monosodium L-glutamate.


Risk factors for complications of percutaneous ultrasound-guided renal biopsy in children.
Percutaneous ultrasound-guided renal biopsy (PURB) is an invasive but essential procedure in establishing the histologic diagnosis of pediatric renal diseases. Large studies which describe PURB complications and its contributory risk factors are scarce in the pediatric literature. Patients who underwent real-time PURB from September 2011 to August 2017 were retrospectively reviewed. Data pertaining to clinical characteristics, histologic diagnosis and biopsy-related complications were collected. In addition, the risk factors for complications were also analyzed. Overall, 183 patients (109 females) were enrolled and 201 biopsies were obtained. The mean age was 14.4 ± 13.7 years. Over 98% of the biopsies were considered adequate in quality. The major complications were perirenal hematoma requiring blood transfusion (4 cases, 2.0%), followed by perirenal abscess (1 case, 0.5%) and arteriovenous fistula (1 case, 0.5%). All patients recovered without sequelae after treatment. Hypertension, low estimated glomerular filtration rate (eGFR) and anemia were more common in patients with complication than in those without. Further logistic regression model analysis demonstrated that eGFR <30 ml/1.73m2/min was an independent risk factor for major complications. Perirenal hematoma needing blood transfusion is the most common major complication for children undergoing renal biopsy. Low eGFR is an independent risk factor for major complications. Early recognition and timely treatment should be delivered to children with renal function impairment accordingly.


Effect of chitosan addition on the properties of low-density polyethylene blend as potential bioplastic.
Plastics based on low-density polyethylene (LDPE) blends generally have limited miscibility, and it is difficult to obtain a homogeneous blend. Although they show excellent properties, their thermal degradation rate is a concern. This work aims to realize a homogeneous blend with higher chitosan concentration, thus expected to increase its degradation properties. An extrusion technique successfully synthesized LDPE and chitosan blends. The mixtures were prepared by adding maleic anhydride (MA) and tert-butyl peroxybenzoate (TBPB) as a compatibilizer and initiator, respectively. The addition of MA and TBPB resulted in homogeneous blends and using chitosan concentration of 40 %wt resulted in better tensile strength and elongation at break. The water uptake increased along with chitosan concentration in the blends. The thermal behavior analysis of the blends conducted by simultaneous TG/DTA revealed that the increase of chitosan concentration tends to improve the blend's thermal degradation slightly. Moreover, chitosan addition resulted in approximately a hundred times larger biodegradability compared to plastics based on LDPE alone.


Immunocytochemical study of somatostatin, neurotensin, GABA, and glycine in rat spinal dorsal horn.
In order to determine whether somatostatin coexists with GABA or glycine in neurones in rat spinal dorsal horn, a combined pre- and post-embedding immunocytochemical study was carried out. One hundred six somatostatin-immunoreactive neurones located in lamina II and the dorsal half of lamina III were tested with antiserum or monoclonal antibody to GABA and none of these cells showed GABA-like immunoreactivity. However, 8 out of 13 somatostatin-immunoreactive neurones located deeper in the dorsal horn (ventral lamina III and lamina IV) showed glycine-like immunoreactivity, and 6 of these were also GABA-immunoreactive. We have previously shown that neurotensin-immunoreactive neurones in laminae II and III are also not immunoreactive when tested with GABA antiserum (Todd et al.: Neuroscience 47:685-691, 1992), and a double-labelling fluorescence method was therefore used to compare the distribution of somatostatin and neurotensin within the superficial dorsal horn. The two types of peptide-immunoreactivity were never found in the same profile. These results suggest that somatostatin and neurotensin are present in different populations of non-GABAergic neurones in rat superficial dorsal horn, but that some somatostatin-containing neurones in the deeper part of the dorsal horn contain glycine, with or without GABA.


Physician recommendations regarding tamoxifen and patient utilization of tamoxifen after surgery for ductal carcinoma in situ.
To date, the impact of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial reported in 1999 on the use of tamoxifen after surgery for ductal carcinoma in situ (DCIS) is unknown. The current study was designed to evaluate the impact of NSABP B-24 on current practices at a comprehensive cancer center. The records of 350 consecutive patients with DCIS who were treated at the authors' institution between July 1999 and June 2002 were obtained from a prospective database and analyzed. Whether patients were offered tamoxifen, whether patients accepted tamoxifen, and the associated reasons were recorded along with tamoxifen-related side effects and patient compliance with therapy. Clinical and pathologic factors were evaluated for their impact on recommendations regarding tamoxifen. Differences were assessed by chi-square analysis. Of the 350 patients, 73 were excluded because of evidence of invasive carcinoma on final pathology review. Of the remaining 277 patients, 166 patients (60%) were offered tamoxifen, and 90 patients (54%) chose to take tamoxifen. Of 111 patients who were not offered tamoxifen, 39 patients (35%) had documented explanations, which included bilateral mastectomy (n = 25 patients), medical reasons (n = 10 patients), and already received tamoxifen for other reasons at the time of diagnosis (n = 4 patients). Of 94 patients who received tamoxifen, 20 patients (21%) discontinued use because of side effects or complications. Tamoxifen was more likely to be recommended for women who underwent segmental resection compared with women who underwent total mastectomy (P = 0.002) and for women with smaller pathologic DCIS tumors (P = 0.001). In addition, these two factors were interrelated. Physicians and patients remain cautious regarding the use of tamoxifen after local treatment for DCIS. The current findings have implications for current trials evaluating aromatase inhibitors and other chemopreventive agents for this disease.


Surgical resection combined with perioperative chemotherapy for a patient with locally recurrent, previously stage IV thymic small-cell carcinoma: A case report.
An 83-year-old Japanese man visited our hospital with dyspnea and general fatigue. Computed tomography (CT) revealed a tumor in the anterior mediastinum, bilateral pleural effusion, pericardial fluid, and multiple liver nodules. We performed a CT-guided tumor biopsy, and the patient was diagnosed with thymic small-cell carcinoma, Masaoka-Koga stage classification IVb. The patient received four cycles of carboplatin and etoposide, and all lesions disappeared on CT. However, after 6 months, CT revealed a recurrent tumor in the anterior mediastinum. After one cycle of rechallenge chemotherapy, we performed extended total thymectomy followed by another three cycles of chemotherapy. More than 2.5 years after the last chemotherapy session, the patient's carcinoma did not recur. Thus, this case suggests that salvage surgery may be a treatment option for local recurrence of thymic carcinoma after complete remission with chemotherapy, even in patients with stage IV cancer.


Intraoperative measurement of choline acetyltransferase activity to evaluate the functional status of donor nerve during reinnervated free muscle transfer: a preliminary report.
Intraoperative choline acetyltransferase activity measurements were used to evaluate the functional status of donor nerves during reinnervated free muscle transfer. This technique was applied to 3 cases. One was a lower-type brachial plexus injury in combination with radial nerve injury; the other 2 were Volkmann's ischemic contractures. Gracilis muscle was transferred for reconstruction of wrist extension in all cases. The donor nerves included 1 anterior interosseous nerve and 2 posterior interosseous nerves. A fascicle with choline acetyltransferase activity above 2,000 cpm was considered to be reliable as a motor fascicle. Reinnervation of transferred muscle was confirmed by electromyographic examination within the first 3.3 months (range, 2.5 to 4 months) after surgery and all muscles obtained useful recovery. This technique can directly and quantitatively verify the functional quality of the donor motor fascicle when the quality of the donor nerve is in doubt.


EGFR, HER2 target based molecular docking analysis, in vitro screening of 2, 4, 5-trisubstituted imidazole derivatives as potential anti-oxidant and cytotoxic agents.
In our endeavor towards the development of potent molecules for cancer diseases, we have designed and synthesized a series of 2,4,5-trisubstituted imidazole derivatives (B1-B24) and characterized by using various spectroscopic techniques. All these compounds are further evaluated for their in vitro anti-cancer, anti-oxidant activities and molecular docking studies against EGFR, HER2 protein receptors. The in vitro anti-cancer activity analysis reveals that compounds B11 and B16 were found to be effective scaffolds against the tested human cancer cell lines IMR-32, A549 and HeLa. Particularly, B16 and B11 showed effective cytotoxicity against A549 and IMR-32 with IC50 values of 09.521±0.54μM and 10.294±0.43μM, respectively. Moreover, compounds B17, B18 and B23 showed potent activity towards the anti-oxidant screening with IC50 values of 5.87±1.73μM, 6.29±1.27μM and 4.95±1.81μM, respectively compared to standard ascorbic acid. Molecular docking was performed against the EGFR, HER2 protein receptors to provide more insight into their mechanism of interaction by comparing with standard EGFR, HER2 inhibitors like Gefitinib (EFGR), Lapatanib (EGFR), Afitinib (HER2) and Canertinib (HER2). Compounds B15, B16, B11 and B10 were exhibiting their minimum binding energies. Out of the aforementioned docked molecules, B15 and B16 showed the best binding energies of -11.15kcalmol-1, -10.70kcalmol-1 and -10.49kcalmol-1, -10.12kcalmol-1 against EGFR and HER2 protein receptors, respectively. The molecular docking results are well corroborated with the in vitro anti-cancer activity finding.


Predicting the Risks of Aggressive-Intent Chemotherapy Toxicity in Older Patients With Lymphoma: A Prospective Observational Pilot Study.
Lymphoma is a disease of older patients and while treatment is subtype specific, curative or aggressive intent combination chemotherapy is often recommended. However, there has been limited evidence on which to base treatment decisions for older adults. Our objectives were to assess the utility of risk stratification measures and serial functional tests in predicting chemotherapy toxicity and as well the feasibility of conducting these in older adults undergoing chemotherapy for lymphoproliferative disorders. This prospective cohort study recruited lymphoma patients 70 years or older planned for systemic chemotherapy. The Cancer and Aging Research Group (CARG) risk stratification tool and Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) were calculated at baseline. The Clinical Frailty Scale (CFS), Charlson Comorbidity Index score, grip strength and gait speed test, and toxicity events, were assessed at baseline and serially throughout treatment. Sarcopenia was calculated on CT scans at baseline, midway through treatment, and 1-month after completion of therapy. The primary endpoint was to assess the feasibility of applying these measures in busy ambulatory clinics. These measures were also correlated with clinical outcomes including ≥grade 3 adverse events (AEs), hospitalizations and emergency department visits, dose changes or delays, and overall survival. In total, 30 patients were enrolled (mean age 78.1 ± 6.4 years), of whom 20 were treated with curative intent. A total of 16 patients (53%) experienced grade ≥3 AEs, 9 (56%) of which led to a chemotherapy delay. On univariable analyses, CFS score, a high CARG score, medium to high CRASH score, and the gait speed were associated with grade ≥3 AEs, while only CFS remained significant on multivariable analysis. On univariable analysis, patients with a medium to high risk CRASH score were more likely than low risk patients to have an unplanned emergency department visit or hospitalization. The CFS seems to predict toxicity in this cohort study, with gait speed, CARG and CRASH scores being potentially additional predictive methods of evaluation.


Kinetics of the inactivation of the protein-lipid complex, firefly luciferase, by sodium deoxycholate and its reactivation by phosphatidylcholine.
Firefly luciferase has been shown to be a protein-lipid complex. Phospholipids and neutral lipids bound to luciferase have been identified. Sodium deoxycholate rapidly inactivated the enzyme, but an excess of phosphatidylcholine recovered luciferase activity. From the kinetics of inactivation and reactivation, a mechanism for interaction of the enzyme with detergents and phospholipids has been proposed. The substrates ATP and Mg2+ stabilized luciferase during delipidation.


Injectable decellularized extracellular matrix hydrogel promotes salivary gland regeneration via endogenous stem cell recruitment and suppression of fibrogenesis.
Saliva is key to the maintenance of oral homeostasis. However, several forms of salivary gland (SG) disorders, followed by hyposalivation, often result in dental caries, oral infection, and decreased taste, which dramatically affect the quality of patient's life. Functional biomaterials hold great potential for tissue regeneration in damaged or dysfunctional SGs and maintaining the good health of oral cavity. Herein, we prepared an injectable hydrogel derived from decellularized porcine submandibular glands (pDSG-gel), the material and biological properties of the hydrogel were systematically investigated. First, good biocompatibility and bioactivities of the pDSG-gel were validated in 2D and 3D cultures of primary submandibular gland mesenchymal stem cells (SGMSCs). Especially, the pDSG-gel effectively facilitated SGMSCs migration and recruitment through the activation of PI3K/AKT signaling pathway, suggested by transcriptomic analysis and immunoblotting. Furthermore, proteomic analysis of the pDSG revealed that many extracellular matrix components and secreted factors were preserved, which may contribute to stem cell homing. The recruitment of endogenous SG cells was confirmed in vivo, upon in situ injection of the pDSG-gel into the defective SGs in rats. Acinar and ductal-like structures were evident in the injury sites after pDSG-gel treatment, suggesting the reconstruction of functional SG units. Meanwhile, histological characterizations showed that the administration of the pDSG-gel also significantly suppressed fibrogenesis within the injured SG tissues. Taken together, this tissue-specific hydrogel provides a pro-regenerative microenvironment for endogenous SG regeneration and holds great promise as a powerful and bioactive material for future treatments of SG diseases. STATEMENT OF SIGNIFICANCE: Decellularized extracellular matrix (dECM) has been acknowledged as one of the most promising biomaterials that recapitalizes the microenvironment in native tissues. Hydrogel derived from the dECM allows in situ administration for tissue repair. Herein, a tissue-specific dECM hydrogel derived from porcine salivary glands (pDSG-gel) was successfully prepared and developed for functional reconstruction of defective salivary gland (SG) tissues. The pDSG-gel effectively accelerated endogenous SG stem cells migration and their recruitment for acinar- and ductal-like regeneration, which was attributed to the activation of PI3K/AKT signaling pathway. Additionally, the introduction of the pDSG-gel resulted in highly suppressed fibrogenesis in the defective tissues. These outcomes indicated that the pDSG-gel holds great potential in clinical translation toward SG regeneration through cell-free treatments.


The role of vascular endothelial growth factor as a prognostic and clinicopathological marker in osteosarcoma: a systematic review and meta-analysis.
In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma. We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma. A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87-3.11, p < 0.001) and disease-free survival (HR, 2.604; 95% CI, 1.698-3.995, p < 0.001), respectively. Furthermore, investigation regarding osteosarcoma clinicopathologic characteristics suggested that high VEGF expression was significantly associated with metastasis (OR, 4.39; 95% CI, 2.77-6.95; p < 0.001), clinical stage (OR, 0.73; 95% CI, 0.62-0.87; p < 0.001), and microvessel density (SMD, 3.33, 95% CI,1.57-5.10, p < 0.001), but not associated with tumor location, gender, age, local recurrence, and chemotherapy response. Our meta-analysis findings suggest that elevated VEGF expression may be a predictive biomarker for poor prognosis and adverse clinicopathological characteristics in patients with osteosarcoma.


Gene expression of NOR-1, a neuron-derived orphan receptor, is inducible in neuronal and other cell lineages in culture.
We recently isolated a cDNA of NOR-1, a novel member of the steroid/thyroid hormone receptor superfamily, from a rat neuronal cell cDNA library. NOR-1 has strong amino acid sequence homology to orphan receptors NGFI-B and Nurr1, and is expressed predominantly in the brain tissue in vivo. In the present study, we examined NOR-1 gene expression in various cultured cells with distinct properties of neuronal cells (PC12), glial cells (C6), endocrine cells (GH3, AtT-20 and Y-1), or fibroblasts (NIH3T3 and L), by reverse transcription-polymerase chain reaction and nucleotide sequencing. NOR-1 transcripts were induced with forskolin and 12-O-tetradecanoylphorbol-13-acetate in all cell lines examined. The nerve growth factor induced not only NGFI-B but also NOR-1 and Nurr1 transcripts in PC12 cells. These findings suggest that NOR-1 gene expression is induced by various stimuli in diverse cell types.


Incorporating prior shape knowledge via data-driven loss model to improve 3D liver segmentation in deep CNNs.
Convolutional neural networks (CNNs) have obtained enormous success in liver segmentation. However, there are several challenges, including low-contrast images, and large variations in the shape, and appearance of the liver. Incorporating prior knowledge in deep CNN models improves their performance and generalization. A convolutional denoising auto-encoder is utilized to learn global information about 3D liver shapes in a low-dimensional latent space. Then, the deep data-driven knowledge is used to define a loss function and combine it with the Dice loss in the main segmentation model. The resultant hybrid model would be forced to learn the global shape information as prior knowledge, while it tries to produce accurate results and increase the Dice score. The proposed training strategy improved the performance of the 3D U-Net model and reached the Dice score of 97.62% on the Sliver07-I liver dataset, which is competitive to the state-of-the-art automatic segmentation methods. The proposed algorithm enhanced the generalization and robustness of the hybrid model and outperformed the 3D U-Net model in the prediction of unseen images. The results indicate that the incorporation of prior shape knowledge enhances liver segmentation tasks in deep CNN models. The proposed method improves the generalization and robustness of the hybrid model due to the abstract features provided by the data-driven loss model.


Incidence of abnormal haemoglobin traits among Gambian children.
The electrophoretic mobility of haemoglobin from 343 Gambian children between the ages of two months and ten years has been investigated. The incidence of Hb-S and Hb-C traits is described and compared with earlier reports on the distribution of these traits in The Gambia. One child was identified as having the rare haemoglobin, Hb-A + N.


Study of neuronal gain in a conductance-based leaky integrate-and-fire neuron model with balanced excitatory and inhibitory synaptic input.
Neurons receive a continual stream of excitatory and inhibitory synaptic inputs. A conductance-based neuron model is used to investigate how the balanced component of this input modulates the amplitude of neuronal responses. The output spiking rate is well described by a formula involving three parameters: the mean mu and variance sigma of the membrane potential and the effective membrane time constant tauQ. This expression shows that, for sufficiently small tauQ, the level of balanced excitatory-inhibitory input has a nonlinear modulatory effect on the neuronal gain.


Enantioselective synthesis of dihydropyridinones via NHC-catalyzed aza-Claisen reaction.
N-Heterocyclic carbene catalyzed aza-Claisen annulations of enals or their α'-hydroxyenone surrogates with vinylogous amides afford dihydropyridinones. The reaction proceeds with a broad range of substrates, and no nitrogen protecting group is required.


The attitude and perception of hospital doctors about the management of psychiatric disorders.
To determine perception and the attitude of non-psychiatric doctors about psychiatric problems working in a tertiary care hospital. Cross-sectional survey. Postgraduate Medical Institute, Lady Reading Hospital, Peshawar. The questionnaires distributed were returned within one week duration. All the doctors working in Lady Reading Hospital, Peshawar for more than one year except house officers and those working in Paediatrics, Radiology and Administration Block were given anonymous questionnaires. Two hundred and ten doctors returned the questionnaires. One hundred and eighty-three (87 %) of respondents were male. Ninty-eight percent of doctors agreed that psychological factors were important in the cause and outcome of physical disorders but only 26.7 % agreed that management of emotional issues is medical responsibility. There was no statistically significant difference between physicians and surgeons in their attitude towards importance of psychological factors in the physical disorders. Doctors working in tertiary care hospital have adequate awareness about the psychological and emotional factors in medical and surgical patients. However, some barriers against the provision of bio-psychosocial care seem to be present.


Activity requirements of epidermolytic toxin from Staphylococcus aureus studied by an in vitro assay.
The activity of epidermolytic toxin from Staphylococcus aureus was studied in vitro using discs of neonatal mouse skin. By assessing the loss of skin integrity as a function of toxin dose and time, it was possible to put the assay on a semi-quantitative basis. Epidermolysis occurred without any change in rate from pH 3.8 to 8.7, and at an increasing rate in the temperature range of 0-37 degrees C. Activity was observed even at the lowest temperature. More than 30 inhibitors of energy metabolism, central metabolic pathways, receptor binding or proteolysis, individually failed to prevent epidermolysis and it is suggested that intoxication cannot be dependent on receptor-mediated endocytosis. Five metal-ion chelators inhibited epidermolysis, due to an effect on the tissue rather than on the toxin. Using X-ray fluorescence and atomic absorption spectroscopy, it was shown that epidermolytic toxins do not contain any essential metal ions. Some transition metals, but not Ca2+ or Mg2+, prevented the chelator-dependent inhibition of epidermolysis.


Radiological incidence of donor-site incisional hernia and parastomal hernia after vertical rectus abdominus myocutaneous flap-based reconstruction following colorectal surgery.
A vertical rectus abdominis myocutaneous (VRAM) flap is commonly used to reconstruct perineal defects for low rectal and anal cancer. The incidence of midline incisional hernias after VRAM reconstruction varies from 3.6% when detected clinically to 50% when detected radiologically. The aim of this study is to accurately determine the radiological incidence of donor-site incisional and parastomal hernia following VRAM reconstruction. This was a retrospective cohort study of patients undergoing colorectal surgery requiring VRAM reconstruction over 10 years. Data were collected on patient demographics, indication for surgery and surgical procedure, including details of any hernia repair. Images from surveillance CTs were reviewed for the presence and size of midline incisional and/or parastomal hernias. Parastomal hernias were classified based on the European Hernia Society (EHS) classification. One hundred and seventy three patients were included in the analysis. The median age was 67 years (range 29-88 years) and the median length of follow-up was 49 months (interquartile range 24.3-71.0 months). The cumulative incidence of donor-site incisional hernia after VRAM at 1, 2 and 5 years was 15.1%, 25.4% and 29.1%, respectively. The cumulative incidence for PSH at 1, 2 and 5 years was 33.1%, 46.6% and 53.3%, respectively (95% CI 45.4%-60.5%). Most patients who develop donor-site incisional hernia and parastomal herniation following VRAM tend to do so within the first 2 years. Although the use of CT imaging improves the diagnosis of donor-site incisional and parastomal hernias, the clinical significance of this is unknown.


Azithromycin Inhibits Macrophage Tumor Necrosis Factor Secretion in Response to Both Azithromycin-Susceptible and Azithromycin-Resistant Pneumococci.
We studied the effect of azithromycin (AZM) on macrophage responses to pneumococci. We found that exposure of pneumococci to AZM led to reduced tumor necrosis factor (TNF) secretion by macrophages; this effect was observed in response to both AZM-susceptible and AZM-resistant (AZM-R) pneumococci.


Blood Pressure and Outcomes in Patients With Different Etiologies of Intracerebral Hemorrhage: A Multicenter Cohort Study.
Background We aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies. Methods and Results A total of 5656 in-hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH-U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as ≥140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1-month survival rate and 3-month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (P<0.001), structural lesion (P<0.001), and undetermined subtypes (P=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose-responsively associated with higher 3-month mortality in hypertensive angiopathy (Ptrend=0.013) and undetermined (Ptrend=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3-month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20-0.65; P<0.001). Similarly, adjusted Cox regression indicated decreased risk of 1-month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24-0.92; P=0.027). Conclusions This study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP-lowering strategy are needed to validate our findings.


The incidence of self-harm ingestions in adolescents and young adults at a tertiary care center.
There has been an increasing incidence of self-harm attempts in recent years in the United States. Particularly concerning, there has been a growing trend of self-harm in the adolescent and young adult population. In order to inform initiatives to address this trend, risk factors and substances used for self-harm need to be clarified. This is a descriptive retrospective observational study on all cases of self-harm poisoning in patients between the ages of 12 and 25 years reported at the state's only tertiary care center from January 2019 through March 2022. There was an increased incidence of 69% for self-harm poisonings for all ages and a 90% increase in ages 12-17 years between the years 2019 and 2021. Fifty percent of all cases occurred in patients aged 14-17 years, 69% were female, and 22% required an intensive care unit. The top three most common substances used are available without a prescription. There was a persistent increase in self-harm attempts via poisoning throughout the study period with a particularly vulnerable period in the adolescent age group.


Long-term clinical results of 33 thumb replantations.
Thumb replantation following complete amputation is a relatively frequent and well-established surgical procedure. In literature many studies report a discrepancy between the objective measurements and the subjective satisfaction of the patients. Nowadays, evaluation of the patient long-term benefit obtained by replantation is uncertain. The aim of this study was to consider the long-term results of 33 thumb replantation procedures. The period considered is from January 1997 to December 2015, 33 subjects fulfilled the study inclusion criteria and were included in the study. We evaluated in each patient: ROM (performing Kapandji test), level and mechanism of amputation, force peak of three grips using Dexter dynamometer (five-handle, key, tri-digital grips), sensibility (using Disk-Criminator and aesthesiometers of Semmes-Weinstein) and subjective perception of disability (using DASH questionnaire). All patients were males, 94% of them returned to their previous occupation. Average follow-up was 9±4 years. The prevalent mechanism of injury was a combined amputation in 58% of cases. Levels involved in more than half of patients were interphalangeal joints and proximal phalanxes. Ratios of strength recovery were: for the five-handle grip equal to 0.90±0.28 kg (p=0.63), 0.78±0.30 kg (p=0.64) for key grip and 0.75±0.32 kg (p=0.78) for tri-digital grip. Results for Kapandji test was 8±2 and for DASH test was 16±21. The protective tactile threshold was recovered in 49% of patients; S2PD test resulted positive in 54% and D2PD test in 39% of cases. Results confirm and strengthen evidence of positive long-term functional outcomes of thumb replantation interventions.


Molecular Characteristics and Gonococcal Genetic Island Carrying Status of Thirty-Seven Neisseria gonorrhoeae Isolates in Eastern China.
To investigate the carrying situation of N. gonorrhoeae genetic island (GGI), and to understand the existence of GGI of different multilocus sequence types (MLST), so as to provide evidence for epidemiology. From January 2018 to December 2020, a total of 37 clinical isolates of N. gonorrhoeae were collected. Resistance to tetracycline, β-lactam, and azithromycin were measured. Genes in GGI (atlA, traG, and traH) were amplified via polymerase chain reaction (PCR). All clinical isolates were subjected to N. gonorrhoeae MLST. The GGI of N. gonorrhoeae were widespread, and the positive detection rates of atlA, traG and traH were all 81.08% (30/37). In this study, atlA, traG and traH were always detected positive together. No significant difference in the positive rate of the GGI between the azithromycin-sensitive and the resistance groups or between the β-lactam positive and negative groups (P > 0.05) was found; however, there was a significant difference between the high-level tetracycline-resistant group and the non-high-level resistant group (P < 0.05), with the carrier rates being 60.00% and 94.45%, respectively. Among the 37 isolates studied, 12 distinct MLST were determined, while MLST ST8123 occurred most frequently, accounting for 18.91% (7/37), followed by ST1928, ST7367 and ST7822, all 13.51% (5/37). N. gonorrhoeae typed as ST1928, ST1901, ST1588 and ST7822, the GGI were all positive. These four types are more likely to become highly virulent strains.


The Role of the T2-FLAIR Mismatch Sign as an Imaging Marker of IDH Status in a Mixed Population of Low- and High-Grade Gliomas.
Our study evaluated the role of the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign in detecting isocitrate dehydrogenase (IDH) mutations based on a mixed sample of 24 patients with low- and high- grade gliomas. The association between the two was realized using univariate and multivariate logistic regression analysis. There was a substantial agreement between the two raters for the detection of the T2-FLAIR mismatch sign (Cohen's kappa coefficient was 0.647). The T2-FLAIR mismatch sign when co-registered with the degree of tumor homogeneity were significant predictors of the IDH status (OR 29.642; 95% CI 1.73-509.15, p = 0.019). The probability of being IDH mutant in the presence of T2-FLAIR mismatch sign was as high as 92.9% (95% CI 63-99%). The sensitivity and specificity of T2-FLAIR mismatch sign in the detection of the IDH mutation was 88.9% and 86.7%, respectively. The T2-FLAIR mismatch sign may be an easy to use and helpful tool in recognizing IDH mutant patients, particularly if formal IDH testing is not available. We suggest that the adoption of a protocol based on imaging and histological data for optimal glioma characterization could be very helpful.


Shape and size control of Ag2Se nanocrystals from a single precursor [(Ph3P)3Ag2(SeC{O}Ph)2].
Monodispersed Ag2Se nanocubes and faceted nanocrystals have been synthesized by hexadecylamine (HDA) induced thermolysis of [(PPh3)3Ag2(SeC{O}Ph)2] in a mixture of TOP (tri-n-octyl phosphine) and HDA in the temperature range 95-180 degrees C.


A comparative study on the diagnostic validity of three scoring systems in the diagnosis of acute appendicitis in emergency centres.
Considering the inconsistencies on the validity scoring systems in the diagnosis of acute appendicitis, our aim was to compare the accuracy of the three Anderson, Alvarado and Alvarado + CRP scoring systems in the diagnosis of patients with suspected acute appendicitis. This was a prospective observational study performed on patients 15-65 years complained of abdominal pain in the RLQ with a high clinical suspicion of acute appendicitis within two years. The scoring systems of Anderson, Alvarado, and Alvarado + CRP were recorded using a pre-prepared questionnaire by a senior emergency medicine assistant. Acute appendicitis was confirmed based on the histopathologic findings. Written informed consent was obtained from all the patients before entering the study. 200 patients were enrolled in the study. In 159 cases diagnosed with appendicitis based on histopathological findings, Anderson, Alvarado, and Alvarado scoring systems were able to identify 121, 152, and 147 cases respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 77%, 19%, 78%, 17 and 64% in Anderson, 95%, 7%, 75%, 30% and 77% in Alvarado, and 92%, 7%, 79%, 20%, and 75% in Alvarado + CRP scoring systems, respectively. Anderson scoring system had lower diagnostic accuracy than the Alvarado system. The role of CRP as an adjunct test to increase the accuracy of the Alvarado scoring system in the diagnosis of acute appendicitis has been under question. Given the inconsistent results of the scoring systems in the diagnosis of acute appendicitis, there is a need to develop a more precise clinical-paraclinical scoring system for this condition.


Phylogenetic diversity and activity screening of cultivable Actinobacteria isolated from marine sponges and associated environments from the western coast of India.
The phylogenetic diversity of cultivable actinobacteria isolated from sponges (Haliclona spp.) and associated intertidal zone environments along the northern parts of the western coast of India were studied using 16S rRNA gene sequences. A subset of randomly selected actinobacterial cultures were screened for three activities, namely predatory behaviour, antibacterial activity and enzyme inhibition. We recovered 237 isolates from the phylum Actinobacteria belonging to 19 families and 28 genera, which could be attributed to 95 putative species using maximum-likelihood partition and 100 putative species using Bayesian partition in Poisson tree processes. Although the trends in the discovery of actinobacterial genera isolated from sponges were consistent with previous studies from different study areas, we provide the first report of nine actinobacterial species from sponges. We observed widespread non-obligate epibiotic predatory behaviour in eight actinobacterial genera and we provide the first report of predatory activity in Brevibacterium , Glutamicibacter , Micromonospora , Nocardiopsis , Rhodococcus and Rothia . Sponge-associated actinobacteria showed significantly more predatory behaviour than environmental isolates. While antibacterial activity by actinobacterial isolates mainly affected Gram-positive target bacteria with little or no effect on Gram-negative bacteria, predation targeted both Gram-positive and Gram-negative prey with equal propensity. Actinobacterial isolates from both sponges and associated environments produced inhibitors of serine proteases and angiotensin-converting enzyme. Predatory behaviour was strongly associated with inhibition of trypsin and chymotrypsin. Our study suggests that the sponges and associated environments of the western coast of India are rich in actinobacterial diversity, with widespread predatory activity, antibacterial activity and production of enzyme inhibitors. Understanding the diversity and associations among various actinobacterial activities - with each other and the source of isolation - can provide new insights into marine microbial ecology and provide opportunities to isolate novel therapeutic agents.


Studying the Effect of a Composition of the Cluster Core in High-Radiopacity Cluster Complexes of Rhenium on Their Acute Toxicity In Vivo.
An in vivo study was performed to evaluate the dependence of acute toxicity of high-radiopacity and luminescent octahedral cluster complexes of rhenium after intravenous injection on a composition of the cluster core. Changes in mouse body weight, water and food consumption, degree of intoxication, and morphological changes in the visceral organs were studied after intravenous injection of the following cluster complexes with various internal ligands (S, Se, or Te): Na4[{Re 6 Te 8 }(CN)6], Na4[{Re 6 Se 8 }(CN)6], and Na4[{Re 6 S 8 }(CN)6]. The Na4[{Re 6 S 8 } (CN)6] cluster complex was shown to be the safest for animals.


Late Holocene droughts and cave ice harvesting by Ancestral Puebloans.
Water availability for Native Americans in the southwestern United States during periods of prolonged droughts is poorly understood as regional hydroclimate records are scant or contradicting. Here, we show that radiocarbon-dated charcoal recovered from an ice deposit accumulated in Cave 29, western New Mexico, provide unambiguous evidence for five drought events that impacted the Ancestral Puebloan society between ~ AD 150 and 950. The presence of abundant charred material in this cave indicates that they periodically obtained drinking water by using fire to melt cave ice, and sheds light on one of many human-environment interactions in the Southwest in a context when climate change forced growing Ancestral Puebloan populations to exploit water resources in unexpected locations. The melting of cave ice under current climate conditions is both uncovering and threatening a fragile source of paleoenvironmental and archaeological evidence of human adaptations to a seemingly marginal environment.


Performance of EUS-FNB in solid pancreatic masses: a lesson from 463 consecutive procedures and a practical nomogram.
The study's main goal was the diagnostic adequacy of pancreatic endoscopic ultrasonographic (EUS) fine-needle biopsy (FNB) and associated predictive factors. The secondary objective was to define the diagnostic accuracy of EUS-FNB in the diagnosis of pancreatic masses and pancreatic malignancies. None of the studies reported the diagnostic adequacy and accuracy of EUS. We retrospectively identified patients with solid pancreatic lesions that underwent EUS-FNB between 2013, and 2018. We calculated diagnostic adequacy and related factors. Using definitive histology on the surgically resected specimen as the gold standard, we calculated diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB. We identified a total of 463 procedures. Diagnostic specimens were adequate in 436 procedures (94.1%), while 27 biopsies provided insufficient samples (5.9%). The multivariate analysis showed that lesion size and needle caliper were the only factors influencing diagnostic adequacy. The use of a biopsy needle (OR 0.69, 95% CI 0.30-0.1.63, P 0.400) did not improve sample adequacy. We calculated sensitivity (100%), specificity (93.2%), diagnostic accuracy (93.2%), positive predictive value (97.1%), and negative predictive value (100%) using resected specimen as the gold standard. We found no significant complications. EUS-FNB is a reliable technique for the histological characterization of solid pancreatic masses.


Diverging lay intuitions about concepts related to free will in arbitrary and deliberate decisions.
Philosophical accounts of free will frequently appeal to deliberate, consequential, and purposeful decisions. However, some recent studies have found that laypeople attribute more freedom to arbitrary than to deliberate decisions. We hypothesized that these differences stem from diverging intuitions about concepts surrounding free will-especially freedom, being in control, and the ability to decide otherwise. In two studies, we found that laypeople attributed high levels of free will, freedom, and control to both arbitrary and deliberate decisions. However, subjects surprisingly attributed reduced ability to decide otherwise when faced with an "easy" decision with one clearly superior option. Furthermore, laypeople attributed greater free will, freedom, and control to "easy" than "hard" decisions with no clearly superior option. Our results suggest that laypeople have diverging intuitions about these different, free-will-related concepts. Therefore, a scientific account of free will may require integrating results from studies on different types of decision-making.


Eccentric cross-exercise after anterior cruciate ligament reconstruction: Novel case series to enhance neuroplasticity.
Substantial changes in neural function are historically present after anterior cruciate ligament reconstruction (ACLR), and are not rectified with traditional rehabilitation. Cross-exercise is a potential means to enhance neural excitability and improve recovery after ACLR. Hence our purpose, was to detail changes in brain activation, neural excitability and patient-reported outcomes in a cohort that completed an 8-week quadriceps-focused eccentric cross-exercise training program immediately following ACLR. Case series. University. Five patients participated in an 8-week (24-session) eccentric cross-exercise intervention after ACLR. Brain activation, neural activity and patient-reported outcomes were evaluated within 2 weeks post-ACLR and again at 10-weeks post-ACLR after the intervention. Each cross-exercise session consisted of 4 sets of 10 isokinetic eccentric contractions at 60 deg/sec with the noninvolved limb. Following the intervention, patients demonstrated a facilitated spinal reflexive and muscle activity response from the motor cortex during a time when these measures are known to be depressed. Patients also demonstrated a reduce dependence on frontal cortex activity to generate quadriceps contractions. Further patients reported significant reductions in pain and symptoms and greater knee function. Eccentric cross-exercise after ACLR helps to facilitate positive adaptations in neural function and patient reported outcomes.


Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice.
During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics was performed comparing the livers of Yorkshire pigs at postnatal day 7 and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins compared with neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1), and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), a newly identified fifth hexokinase associated with glucose disturbances in pregnant women, was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.


Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning.
Hypercortisolism [ corrected] impairs trace classical conditioning of the eyeblink response to an air puff but does not affect delay conditioning. The opposite neurohormonal condition, hypocortisolism, may facilitate trace classical conditioning, which might be informative in understanding the role of classical conditioning in stress-sensitive syndromes such as fibromyalgia. Volunteers (n = 82) were randomized to receive either an inhibitor of cortisol production (metyrapone, 1500 mg) or placebo and to complete a delay or a trace eyeblink conditioning protocol (unconditioned stimulus: corneal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 75 dB, 1000 Hz, 400 ms; empty interval in trace conditioning: 600 ms), where conditioned eyeblink response probability was assessed electromyographically. Metyrapone induced hypocortisolism, reflected by a 30% decrease of salivary cortisol levels (p < 0.01), and facilitated trace eyeblink conditioning (p < 0.001), while delay eyeblink conditioning remained unaffected. Moreover, extinction of delay-conditioned eyeblink responses was impaired (p = 0.023), but extinction of trace-conditioned responses remained unaffected. We conclude that acute mild metyrapone-induced hypocortisolism facilitates hippocampus-mediated classical trace eyeblink conditioning but suppresses the extinction of cerebellum-based delay-conditioned responses. Both results may be of theoretical and clinical significance for the generation and persistence of psychosomatic symptoms in patient groups characterized by relative hypocortisolism (e.g., fibromyalgia and chronic fatigue).


[Erythropoiesis in iron deficiency].
The kinetics of erythroblast proliferation were studied by means of quantitative 14C-autoradiography in 5 patients showing anemia due to infection or malignancy, in 7 patients suffering from iron deficiency anemia, and in two individuals with bleeding enemia. Compared with a group of 5 healthy persons a markedly reduced turnover of erythroblasts was found in the anemia due to infection, malignancy, and iron deficiency, whereas this turnover was normal or increased in the case of bleeding anemia. The reduction is caused by a progressively decreasing rate of erythroblast proliferation and maturation with advancing development into mature cells. No indications of a change in the number of cell divisions were found in the anemia of infection, malignancy, and of iron deficiency, nor was there evidence of an intramedullary death of nucleated red cell percursors. The imbalance between production and loss of red cells causing anemia shows a different pattern in the 3 groups of disease: In bleeding anemia the insufficiency of supply is not yet apparent from the rate of erythroblast turnover giving weight to the factor of blood loss. In anemia due to infection, malignancy, and iron deficiency the but moderately increased rate of red cell destruction cannot be compensated because of several impairments: The rate of erythroblast turnover is reduced, and, in addition, a moderate portion of maturing cells is destroyed, probably at the reticulocyte stage. As the most significant factor, the bone marrow is unable to compensate the anemia by an effective erythroblast hyperplasia. In iron deficiency this hyperplasia is inadequately low, in infection and malignancies, however, it is more or less missing.


Genetic diversity and drug resistance of Mycobacterium tuberculosis in Ecuador.
The genetic diversity of Mycobacterium tuberculosis in Quito, Ecuador is not well known. To investigate mutations related to drug resistance and bacterial genotypes in M. tuberculosis strains in Ecuador. This was a retrospective study of M. tuberculosis isolates from 104 patients. Isolates were phenotypically resistant to rifampicin (RMP) and/or isoniazid (INH). The genotype was determined using 24-locus mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). Isolates showed mutations in the rpoB and katG genes, and the inhA promoter. In rpoB, we found 13 genetic alterations at codons 511, 513, 514, 515, 516, 526 and 531. Forty-six (44.2%) RMP-resistant isolates belonged to codon 531. In katG, there were nine genetic alterations at codons 296, 312, 314, 315, 322, 324 and 351. Fifty-three (51%) INH-resistant isolates belonged to codon 315. Five mutations not previously described were identified in katG: Thr324Ser, Thr314Ala, Ala312Pro, Trp351Stop and deleted G at 296 codon. The Latin American Mediterranean (LAM) (33.7%) and Ghana (30.8%) lineages presented most of the main mutations observed. This is the first report from Ecuador; it describes five new mutations in katG and indicates that LAM is the most prevalent lineage.


Alkylsilyl derivatives for gas chromatography.
Alkylsilyl reagents are the most widely used reagents for the derivatization of polar compounds containing labile hydrogen atoms for gas chromatography. In this article the reagents and reaction conditions for the formation of trimethylsilyl, alkyldimethylsilyl (particularly t-butyldimethylsilyl), cyclic siliconides, haloalkyldimethylsilyl, and flophemesyl (pentafluorophenyldimethylsilyl) derivatives for a wide range of functional groups are reviewed. The importance of steric hindrance on reaction rates and completion, choice of reaction conditions, stability of derivatives, and options for selective detection are described.


Mortality risk in post-operative head and neck cancer patients during the SARS-Cov2 pandemic: early experiences.
The objective of this report is to outline our early experience with head and neck cancer patients in a tertiary referral center, during the SARS-Cov2 pandemic, and to describe the poor outcomes of patients who acquired the infection. In this case series from a single-center, national tertiary referral center for head and neck cancer we describe three consecutive head and neck cancer patients who contracted SARS-Cov2 during their inpatient stay. Of the three patients described in our case series that contracted SARS-Cov2, two patients died from SARS-Cov2 related illness. We have demonstrated the significant implications that SARS-Cov2 has on head and neck cancer patients, with 3 patients acquiring SARS-Cov2 in hospital, and 2 deaths in our that cohort. We propose a complete separation in the location of where these patients are being managed, and also dedicated non-SARS-Cov2 staff for their peri-operative management. IV.


Correction to: Obesity: a Ghost at the Feast of the Sustainable Development Goals.
A Correction to this paper has been published: https://doi.org/10.1007/s13679-020-00417-7.


Polyethylene glycol 3350 without electrolytes: a new safe, effective, and palatable bowel preparation for colonoscopy in children.
To assess safety, efficacy, and acceptance of polyethylene glycol 3350 without electrolytes (PEG) for bowel preparation for colonoscopy in children. Study design In a prospective study, 46 children (mean age, 11.2 years; range, 2.8-17.8) were given PEG at a dose of 1.5 g/kg/day for 4 days before colonoscopy. Patients were allowed to mix PEG in the beverage of their choice. Stool frequency and adverse effects were monitored during PEG therapy. Compliance, tolerance, and quality of colonic preparation were assessed. Serum electrolytes were measured before and after PEG therapy in 29 children. Daily stool frequency increased with PEG therapy from baseline of 2.6+/-0.3 to 3.0+/-0.5 on day 1, 4.6+/-0.4 on day 2, 5.5+/-0.7 on day 3, and 6.0+/-0.6 on day 4 (days 2, 3, and 4, P<.001 for difference vs baseline). The colonic preparations were rated as excellent or good in 91% and 95% in the right and left colon, respectively, at endoscopy. Adverse effects were mild nausea (13%), abdominal pain (11 %), and vomiting (11%). Electrolyte profile revealed small, clinically insignificant changes with PEG therapy. Compliance and tolerance were rated as excellent by 89% and 85% of patients, respectively. Electrolyte-free PEG 3350 can be used as an effective and safe bowel preparation that is well accepted by children for colonoscopy.


Ultrasonic diagnosis and follow-up of malignant brain tumors in childhood. A report of 4 cases and a review of the literature.
Four patients between the ages of 2 and 20 years with malignant brain tumors were given several sonographic examinations, using an operative calvarial defect or sutural diastasis as an acoustic window. Three of our cases and 86% of cases with malignant brain tumors reported in the literature are echogenic, making possible primary sonographic diagnosis of tumor recurrence and echographic monitoring of tumor therapy.


Quetelet and the emergence of the behavioral sciences.
Adolphe Quetelet was one of the most prominent figures of the second half of the nineteenth century, yet in present-day histories of several social sciences the impact of his ideas is widely ignored. The first part consists of a sketch of his life and work. Astronomer and statistician, he sought to apply the mathematical tools of astronomy to create was has been called a 'mathematics of society'. In particular he demonstrated regularities in the incidence of various social phenomena, notably crime, whose implications were widely debated. In the second part the influence he exerted on some key figures in the then emerging social sciences is traced in some detail; these figures include Durkheim, Galton, Marx, and Tylor. He also advocated the wider use of statistics and his call had a powerful impact on the then emerging fields such as administration, economics, sociology and psychology. He influenced some of his most famous contemporaries, including Florence Nightingale, Karl Marx and Francis Galton.


Inhibition of arachidonic acid release by nordihydroguaiaretic acid and its antioxidant action in rat alveolar macrophages and Chinese hamster lung fibroblasts.
The ability of nordihydroguaiaretic acid (NDGA) to inhibit arachidonic acid (AA) release from rat alveolar macrophages treated with t-butyl hydroperoxide (tBOOH) or from Chinese hamster lung fibroblasts (V79 cells) treated with linoleic acid hydroperoxide (LOOH) was examined. Treatment of alveolar macrophages with 100 microM tBOOH significantly increased arachidonic acid release and its conversion to metabolites. Pretreatment of macrophages with NDGA (greater than or equal to 2.5 microM) inhibited the release of AA and its subsequent metabolism following addition of tBOOH. Treatment of V79 cells with 1 microM LOOH stimulated the release of AA. Pretreatment with either 1 or 10 microM NDGA prior to the addition of LOOH inhibited the release of AA. A23187 (2 microM)-stimulated release of AA from V79 cells was less sensitive to NDGA inhibition. Pretreatment with 10 microM NDGA, but not with 1 microM NDGA, inhibited A23187-stimulated release of AA. PLA2-dependent hydrolysis of micelle preparations of disaturated phosphatidylcholine was not inhibited by NDGA. Previous studies have suggested that the addition of peroxides alters cells by inducing lipid peroxidation so that the action of phospholipases upon their membranes is enhanced. The results suggest that NDGA, a lipid-soluble antioxidant which traps free radicals, indirectly blocked the action of phospholipases upon cell membranes by inhibiting lipid peroxidation.


Quality of life for ventilator-dependent ALS patients and their caregivers.
Seven ventilator-dependent ALS patients and eleven caregivers were interviewed in order to assess the impact of ventilator-dependence on patients and their families. The ALS Care Database questionnaires were administered with special attention to components derived from the Health Status Survey (SF-12) and ALS Quality-of-Life Index (ALSQLI) as well as the ALS Patient Caregiver Form. Six patients had difficulty communicating and one patient was totally unable to communicate. Patients had maximal limitation of daily activities as measured by The ALS QLI, yet a self-reported satisfactory quality-of-life. Caregivers were heavily burdened and their outside activities were severely limited.


Ginkgo leaf extract and dipyridamole injection as adjuvant treatment for acute cerebral infarction: Protocol for systemic review and meta-analysis of randomized controlled trials.
Acute cerebral infarction (ACI) is one of the most commonly seen cerebral vascular disease and the current therapy options are not satisfied. Ginkgo leaf extract and dipyridamole injection (GDI) is widely used as adjuvant therapy for ACI. However, there is no systemic review and meta-analysis published regarding the efficacy and safety of GDI. Herein, we describe the protocol of a proposed study aims to systemically evaluate the efficacy and safety of GDI in ACI patients. Five electronic databases (Medline, EMBase, Cochrane database, China National Knowledge Infrastructure, and Wanfang database) will be searched up to February 28, 2018. Randomized controlled trials (RCTs) meet the eligibility criteria will be identified and included. Data synthesis will be run using RevMan software after the data extraction and risk of bias assessment of included studies. The primary outcomes of this study are effective rate and adverse event rate. This study will provide a high-quality synthesis of RCTs on the efficacy and safety of GDI as an adjuvant therapy in the treatment of ACI. This systemic review and meta-analysis will provide high quality evidence to evaluate GDI as adjuvant therapy in patients with ACI.Registration: PEROSPERO CRD42018107112.


Integrating C4 photosynthesis into C3 crops to increase yield potential.
The growth rate of the human population is faster than improvements in crop yields. To feed people in the future, multiple strategies are required. One proposed approach is to raise the yield potential of C(3) crops by modifying photosynthesis to the more efficient C(4) pathway. Owing to complex changes associated with C(4) photosynthesis, it is no understatement to define this conversion as one of the Grand Challenges for Biology in the 21st Century. Here we outline the challenges of installing a C(4) system and assess how new approaches and knowledge may help achieve this goal.