Pediatric endoscopic pilonidal sinus treatment (PEPSiT): report of a multicentric national study on 294 patients.
This study aimed to report a multicentric national experience about the outcomes of pediatric endoscopic pilonidal sinus treatment (PEPSiT). The medical records of all pediatric patients, aged up to 18 years, who underwent PEPSiT in the period 2019-2021, were retrospectively reviewed. Patients' demographics, operative details, and post-operative outcomes were assessed. A total of 294 patients (182 boys), with median age of 14 years (range 10-18), receiving PEPSiT in the study period, were enrolled. Pilonidal sinus disease (PSD) was primary in 258 (87.8%) and recurrent in 36 (12.2%). The median operative time was 36 min (range 11-120). The median VAS pain score was 0.86 (range 0-3) and the median duration of analgesic use was 27 h (range 12-60). The overall success rate was 95.2% (280/294) and the median time to full healing was 23.4 days (range 19-50). Six/294 (2.0%) patients developed Clavien 2 post-operative complications. The recurrence rate was 4.8% (14/294) and all recurrences were re-operated using PEPSiT. Redo-surgery for wound debridement was performed in one (0.3%) patient with late healing. On multivariate analysis, hirsutism and typology of sinus (pits ≥ 2, paramedian and more proximal to the anus) were predictors of PSD recurrence (p = 0.001). To date, this is the largest series of PEPSiT published in the pediatric population. The outcomes reported after a 3 years experience confirm that PEPSiT is a safe, effective, and real minimally invasive procedure to treat adolescents with PSD. It provides patients quick and painless recovery, satisfactory success, and high quality of life.


Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.
Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations.


X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular failure?
We present the clinical and hormonal findings of a young male with X-linked adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency since the age of 5 years, developed progressive neurological symptoms at the age of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty acids (VLCFAs) and genetic testing. His sexual body hair was sparse. Hormonal investigations revealed normal testosterone and inappropriately elevated LH levels. Androgen receptor gene analysis was negative for mutations or polymorphic variants associated with decreased receptor activity. Signs of hypogonadism in patients with confirmed X-ALD are not exclusively due to primary testicular failure. Tissue specific androgen resistance represents an alternative possibility. Since no loss-of-function mutations were detected in the androgen receptor, it is speculated that the patient's androgen resistance could be part of a functional defect mediated through VLCFA accumulation at the testosterone receptor and/or post-receptor levels.


The pharmacodynamics of tinzaparin in healthy volunteers.
We report the pharmacodynamic properties of tinzaparin (175 U/kg antifactor Xa) given as a single daily administration for 5 consecutive days to 14 healthy volunteers as a known safe, effective treatment of deep vein thrombosis and pulmonary embolism. The Cmax for antifactor Xa (0.87 +/- 0.15 U/ml) was associated with a 2.4 +/- 0.5-fold prolongation of the activated partial thromboplastin time (APTT) and a high antithrombin activity (0.38 +/- 0.1 U/ml). The Cmax value of antifactor Xa was 1.5- and twofold lower than those generated by similar doses of nadroparin and enoxaparin respectively. The clearance of antifactor Xa activity (1.29 +/- 0.2 l/h) was 1.5- and twofold greater than those reported for nadroparin and enoxaparin respectively. These results indicated that the antithrombotic and prohaemorrhagic effects of a low molecular weight heparin were independent from the absolute levels of antifactor Xa activities and from the prolongation of the APTT.


Hybrid palliation versus nonhybrid management for a multi-institutional cohort of infants with critical left heart obstruction.
To compare patient characteristics and overall survival for infants with critical left heart obstruction after hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) versus nonhybrid management (eg, Norwood, primary transplantation, biventricular repair, or transcatheter/surgical aortic valvotomy). From 2005 to 2019, 1045 infants in the Congenital Heart Surgeons' Society critical left heart obstruction cohort underwent interventions across 28 institutions. Using a balancing score propensity analysis, 214 infants who underwent hybrid palliation and 831 infants who underwent nonhybrid management were proportionately matched regarding variables significantly associated with mortality and variables noted to significantly differ between groups. Overall survival between the 2 groups was adjusted by applying balancing scores to nonparametric estimates. Compared with the nonhybrid management group, infants who underwent hybrid palliation had lower birth weight, smaller gestational age, and higher prevalence of in-utero interventions, noncardiac comorbidities, preoperative mechanical ventilation, absent interatrial communication, and moderate or severe mitral valve stenosis (all P values < .03). Unadjusted 12-year survival after hybrid palliation and nonhybrid management, was 55% versus 69%, respectively. After matching, 12-year survival after hybrid palliation versus nonhybrid management was 58% versus 63%, respectively (P = .37). Among matched infants born weighing <2.5 kg, 2-year survival after hybrid palliation versus nonhybrid management was 37% versus 51%, respectively (P = .22). Infants born with critical left heart obstruction who undergo hybrid palliation have more high-risk characteristics and anatomy versus infants who undergo nonhybrid management. Nonetheless, after adjustment, there was no significant difference in 12-year survival after hybrid palliation versus nonhybrid management. Mortality remains high, and hybrid palliation confers no survival advantage, even for lower-birth-weight infants.


The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia.
Two patients and 28 others in the literature were ascertained because of congenital vaginal agenesis associated with clinical and/or radiographic evidence of malformations derived from the cervicothoracic somites. In these patients, there was a high incidence of Müllerian duct aplasia/hypoplasia (96%), renal agenesis and/or ectopy (80%), and abnormalities related to cervicothoracic somite dysplasia, particularly 2 to 4 anomalous vertebrae located between C5-T1 (80%). These consistent findings suggest a distinctive non-random association of malformations: Müllerian duct (MU) aplasia, renal (R) aplasia, and cervicothoracic somite (CS) dysplasia (MURCS). Identification of one component of the MURCS association suggests the presence of the other associated anomalies. A hypothesis for the embryogenic pathogenesis of the MURCS association is proposed which attributes the malformations to an alteration of the blastemas of the lower cervical-upper thoracic somites, arm buds, and pronephric ducts, all of which have an intimate spatial relationship at the end of the fourth week of fetal life. A presently unidentified teratogen may be one of the possible causes of the MURCS association on the basis of a lack of familial transmission, normal chromosomal studies, and the similar effects of a known teratogen (thalidomide) on the developing genitourinary tract.


Ultrastructural localization of acid phosphatase activity in the jejunal absorptive cells of fasted rats.
Ultrastructural localization of acid phosphatase activity was investigated in the jejunal absorptive cells of 21 d fasted rats (about 500 g). The enzyme activity was localized on the membrane of microvilli, the lateral cell membrane, the Golgi complex, the lysosomes and the GERL of Novikoff (a part of the smooth surfaced endoplasmic reticulum located in close proximity to the Golgi saccules) of jejunal absorptive cells. Moreover, the lysosomes of various sizes and shapes with acid phosphatase activity was characteristically encountered in the infranuclear cytoplasm. The lysosomes appeared to be autolysosomes .


Ectopic expression of the human adenine nucleotide translocase, isoform 3 (ANT-3). Characterization of ligand binding properties.
The adenine nucleotide translocase (ANT) is a key component in maintaining cellular energy homeostasis, and has also been implicated in formation of the mitochondrial permeability transition pore. Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line. Overexpression resulted in a concomitant decrease in the endogenous ANT content, allowing for the characterization of binding of known ANT ligands to the human protein. Binding affinities for bongkrekic acid (BKA), ADP, and atractyloside (ATR) were measured in mitochondria from the human ANT-3 expressing cell line, and compared to similar preparations from bovine heart mitochondria by use of a novel radioiodinated derivative of ATR. Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria. Characterizations such as these of human ANT isoforms may lead to drug development for enhanced mitochondrial function and cellular viability.


Possible alpha-adrenergic involvement in nicotine induced alteration of spermatogenesis in rat.
Nicotine caused a fall in primary spermatocyte number together with a retardation of spermatocyte to spermatid conversions process. These effects of nicotine were possibly secondary to increased activity of adrenomedullary catecholamines, since the antispermatogenic effect of nicotine was prevented by phentolamine, a known blocker of catecholamine action at the alpha-receptor level.


Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity.
Clinical data have been equivocal and controversial as to the benefits to the brain and cognition of hormone therapy (HT) in postmenopausal women. Recent reevaluation of the role of estrogens proposed that HT may effectively prevent the deleterious effects of aging on cognition, and reduces the risks of dementia, including Alzheimer's disease, if initiated early at the beginning of menopause. Yet, little is known about the effects of HT on brain activation related to cognitive control, the ability to make flexible decisions in relation to internal goals. Here, we used fMRI to directly test for a modulation of sequential 17β estradiol (2 mg/day) plus oral progesterone (100 mg/day) on task switching-related brain activity in women at early postmenopause. The results showed that HT enhanced dorsolateral prefrontal cortex recruitment during task switching. Between-subjects correlation analyses revealed that women who engaged more the dorsolateral prefrontal cortex showed higher task switching performance after HT administration. These results suggest that HT, when taken early at the beginning of postmenopause, may have beneficial effect on cognitive control prefrontal mechanisms. Together, these findings demonstrate that HT can prevent the appearance of reduced prefrontal cortex activity, a neurophysiological measure observed both in healthy aging and early dementia.


Transcriptome-based analysis of the toxic effects of aluminum chloride exposure on spermatocytes.
Aluminum chloride (AlCl3) exposure is pervasive in our daily lives. Numerous studies have demonstrated that exposure to AlCl3 can lead to male reproductive toxicity. However, the precise mechanism of action remains unclear. The objective of this study is to investigate the mechanism of aluminum-induced toxicity by analyzing the alterations in the global transcriptome gene profile of mouse spermatocytes (GC-2spd cells) exposed to AlCl3. GC-2spd cells were exposed to concentrations of 0, 1, 2, and 4 mM AlCl3, and high-throughput mRNA-seq was performed to investigate the changes in the transcriptome after exposure to 4 mM AlCl3. Our findings indicate that exposure to AlCl3 led to an increase in oxidative stress, disrupted glutathione metabolism, reduced cell viability, and altered gene expression in mouse spermatocytes. Gene enrichment analysis revealed that the differentially expressed genes (DEGs) were associated with various biological functions such as mitochondrial inner membrane, response to oxidative stress. Furthermore, these DEGs were found to be enriched in pathways including proteasome, glutathione metabolism, oxidative phosphorylation, and Hif-1 signaling pathway. Real-time PCR and western blot were employed to validate the expression alterations of pivotal genes, and the outcomes exhibited concordance with the mRNA-seq findings. This study provides a theoretical basis for revealing the potential mechanism of male reproductive toxicity caused by aluminum exposure.


Clinical outcomes of combined necrotizing pancreatitis versus extrapancreatic necrosis alone.
Extrapancreatic necrosis (EPN) alone, i.e., in the absence of pancreatic parenchyma necrosis has gradually come to be regarded as a separate entity of acute necrotizing pancreatitis (ANP). However, data regarding the prognostic significance of EPN are quite limited, and the outcomes of interventions for patients with EPN alone are not well elucidated. The aim of this study was to explore the differences in the outcomes of patients with EPN alone and patients with both the pancreatic parenchyma and extrapancreatic necrosis (combined necrosis). From January 2009 to December 2013, a total of 334 patients with ANP who had received interventions in the West China Hospital in China were included. Based on the extent of necrosis as assessed with contrast-enhanced CT, the patients were divided into Group 1 (n = 285) in which the necrosis involved both the pancreatic parenchyma and extrapancreatic tissues (combined necrosis) and Group 2 (n = 49) in which the necrosis involved only the extrapancreatic tissues. Additionally, Group 3 included 443 patients with interstitial pancreatitis who were also included in the analyses. The demographic characteristics, support treatment information, organ failure information, infection necrosis, persistent systemic inflammatory response syndrome (SIRS) in the first week of onset, CT severity index, and intervention types, as well as the postoperative stay lengths, ICU utility, and complications were collected and compared. Compared with the patients in Group 1, the patients in Group 2 suffered less persistent SIRS in the first week of onset (12/24.5% vs. 145/50.9%; P < 0.05), less persistent organ failure (6/12.2% vs. 95/33.3%; P < 0.05), less persistent multiple organ failure (3/6.1% vs. 67/23.5%; P < 0.05), and less bacteremia (5/10.2% vs. 107/37.5%; P < 0.001). The intervention types were significantly different between the two groups (P < 0.001); initial open necrosectomy was performed in 174/61.6% and 8/16.3% of the patients in Groups 1 and 2, respectively, and initial percutaneous catheter drainage (PCD) was performed in 73/25.6% and 29/59.2% of the patients in the two respective groups. Second open necrosectomies following PCD were required in 61/83.5% and 9/31.0% of the patients in Groups 1 and 2, respectively (P < 0.001). A greater number of patients in Group 1 were diagnosed with infected necrosis (204/71.6% vs. 10/20.4%; P < 0.001) and had to be sent to the ICU for further postoperative care (221/77.5% vs. 23/46.9%; P < 0.001). The postoperative stay was longer for Group 1 (median: 43.0 vs. 26.5 days; P < 0.001). Residual necrotic tissue or abscess was the most common postoperative complication in both groups. The mortality was higher in Group 1 (52/18.2% vs. 1/2.1%; P < 0.05). Compared with the patients in Group 2, the patients with interstitial pancreatitis exhibited milder courses and better outcomes. Subgroup comparisons with Group 1 indicated that early multiple organ failure was significantly associated with higher mortality. The patients with EPN alone exhibited significantly better prognoses than those with combined necrosis, and EPN alone should be regarded as a separate group of acute necrotizing pancreatitis. Open necrosectomy can be avoided in the majority of patients with EPN alone, who receive PCD as the initial first intervention.


Drug GRADE: An Integrated Analysis of Population Growth and Cell Death Reveals Drug-Specific and Cancer Subtype-Specific Response Profiles.
When evaluating anti-cancer drugs, two different measurements are used: relative viability, which scores an amalgam of proliferative arrest and cell death, and fractional viability, which specifically scores the degree of cell killing. We quantify relationships between drug-induced growth inhibition and cell death by counting live and dead cells using quantitative microscopy. We find that most drugs affect both proliferation and death, but in different proportions and with different relative timing. This causes a non-uniform relationship between relative and fractional response measurements. To unify these measurements, we created a data visualization and analysis platform called drug GRADE, which characterizes the degree to which death contributes to an observed drug response. GRADE captures drug- and genotype-specific responses, which are not captured using traditional pharmacometrics. This study highlights the idiosyncratic nature of drug-induced proliferative arrest and cell death. Furthermore, we provide a metric for quantitatively evaluating the relationship between these behaviors.


High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets.
Previous research in healthy volunteers has demonstrated that rifampicin and adjusted doses of lopinavir/ritonavir soft-gel capsules resulted in adequate exposure to lopinavir. Our objective was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets. A total of 40 healthy volunteers were planned to start with 600 mg rifampicin once daily from days 1-5. From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily. A 12 h pharmacokinetic curve was planned on day 15. Safety assessments were conducted regularly throughout the study period. Eleven volunteers started as the first group in this study. No major complaints occurred during day 1-5 (rifampicin only). After addition of lopinavir/ritonavir, eight volunteers suffered from both nausea and vomiting, one from nausea only, and one from vomiting only. On day 7, increases in aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were reported in all volunteers and on day 8, the study was prematurely terminated. The AST/ALT levels continued to rise and peaked (grade 2, n = 2; grade 3, n = 1; grade 4, n = 8) on days 9-10. All values returned to normal within 6 weeks. The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin. In the future, this drug combination should not be given to healthy volunteers. Liver function should be carefully monitored when rifampicin and lopinavir/ritonavir are combined in patients.


A probable case of hepatitis B virus transfusion transmission revealed after a 13-month-long window period.
Transfusion-transmitted hepatitis B virus (HBV) infection in recipients with drug-related immunodeficiency is rarely described in endemic areas. Hepatitis B surface antigen (HBsAg)-negative infectious donor blood can be identified by sensitive nucleic acid testing (NAT). Two immunodeficient patients who received blood components from a single seronegative blood donor subsequently found to contain HBV DNA are described. Multiple samples from the implicated donor and the two recipients were tested for HBV serologic and molecular markers. HBV genome fragments were amplified, sequenced, and phylogenetically analyzed. The implicated donation had low-level HBV DNA due to the donor being in the window period before the donor's seroconversion. Recipient 1 had been vaccinated to HBV and carried anti-HBs but remained negative for all other HBV markers until she developed acute hepatitis B (viral load 2.7 x 10(8) IU/mL and alanine aminotransferase [ALT] level 1744 IU/L) 13 months after transfusion of red cells. Identical HBV sequences from both donor and recipient provided evidence of transfusion-related infection. Recipient 2, who received platelets from the same donation while receiving major chemotherapy, remained uninfected. In unusual circumstances, HBV incubation time can be considerably prolonged. Both active and passive neutralizing antibodies to HBV likely delayed, but did not prevent, acute infection when the immune system was impaired. HBV NAT may have interdicted the infectious unit, although the donation viral load could not be quantified and odds of detection calculated.


Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha) from Australian dasyatid and rhinobatid rays.
Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha: Eutetrarhynchidae) is described from the spiral valves of the rays Rhinobatos typus (Rhinobatidae) and Himantura fai (Dasyatidae) from Heron Island, Queensland, Australia. The new species is distinguished from all congeners by the deltoid microtriches covering the anterior 80% of the scolex and the presence of a dorsoventrally elongate genital atrium. The species occurred in the anteriormost section of the spiral valve of R. typus. The orientation of the armature of this and other congeners is such that principal rows of hooks begin on the bothridial surface of the tentacle and end on the antibothridial surface.


Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes.
Many tumours express relatively high levels of low-density lipoprotein (LDL) receptors on their membranes. The LDL receptor is, therefore, an attractive target for the selective delivery of antineoplastic drugs to tumour cells. We reported previously on the synthesis of small apolipoprotein E (apoE)-containing liposomes that behave in vivo in a very similar way to native LDL. In this study, we examined the interaction of this liposomal carrier with cultured B16 melanoma cells. Binding of apoE liposomes to the cells is saturable, with a maximum binding of approximately 90000 particles per cell. Cross-competition studies indicated that apoE liposomes are bound by the LDL receptor. Association of apoE liposomes to B16 cells is strictly Ca2+ dependent, which forms additional evidence for a role of the LDL receptor. The affinity of apoE liposomes for the LDL receptor on B16 cells is 15-fold higher than that of LDL (0.77 vs 11.5 nM respectively). ApoE is essential for the LDL receptor recognition because liposomes lacking apoE were, in competition studies, 20- to 50-fold less effective than apoE-containing liposomes. We examined in B16 tumour-bearing mice the tumour-localizing properties of apoE liposomes and the disposition of an incorporated lipophilic derivative of daunorubicin (LAD). Tissue distribution studies showed that LAD-loaded apoE liposomes were taken up and processed by the major LDL receptor-expressing organs (i.e. adrenals, liver and spleen). Of all other tissues, the tumour showed the highest uptake. The distribution patterns of LAD-loaded apoE liposomes and native LDL in the tumour-bearing mice were very similar, which supports the role of the LDL receptor in the disposition of the prodrug-loaded particles. The disposition of LAD followed the pattern of the liposomal carrier. We conclude that apoE liposomes enable LDL receptor-mediated specific delivery of antineoplastic (pro)drugs to tumours, and, therefore, constitute an attractive novel option for anti-tumour chemotherapy.


Prevalence of heart failure and left ventricular dysfunction in China: the China Hypertension Survey, 2012-2015.
Heart failure (HF) is a major health burden worldwide. However, there is no nationwide epidemiological data on HF in China after 2000. The aims of this study are (i) to determine the prevalence of left ventricular (LV) dysfunction and HF (with reduced, mid-range, and preserved ejection fraction) in a nationally representative Chinese population, and (ii) to investigate the treatment and control of hypertension in HF patients. Data from the China Hypertension Survey (CHS) and 22 158 participants were eligible for analysis in this study. For each participant, a self-reported history of HF and any other cardiovascular diseases was acquired. Two-dimensional and Doppler echocardiography was used to assess LV dysfunction. Overall, 1.3% (estimated 13.7 million) of the Chinese adult population aged ≥35 years had HF, 1.4% of participants had LV systolic dysfunction (ejection fraction <50%), and 2.7% were graded as having 'moderate' or 'severe' LV diastolic dysfunction. The weighted prevalence of HF was similar between urban and rural residents (1.6% vs. 1.1%, P = 0.266), and between men and women (1.4% vs. 1.2%, P = 0.632). In addition, among HF patients with hypertension, 57.7% received antihypertensive medication, and 14.5% had their blood pressure controlled <140/90 mmHg. In summary, there was an increase in the prevalence of HF, and LV dysfunction was very common in China. However, treatment and control of hypertension in participants with HF were low. ChiCTR-ECS-14004641.


Plasma analysis of alpha-difluoromethylornithine using pre-column derivatization with naphthalene-2,3-dicarboxaldehyde/CN and multidimensional chromatography.
A procedure for the plasma analysis of alpha-difluoromethylornithine (DFMO) has been developed that utilizes pre-column derivatization with naphthalene-2,3-dicarboxaldehyde/cyanide (NDA/CN) in pH 9.2 borate buffer. Selective derivatization of delta-amine of DFMO followed by quenching of the reaction results in the formation of a cyanobenz [f] isoindole (CBI) derivative that is stable for 24 h. Plasma was prepared for derivatization by a single step procedure which resulted in an ultrafiltrate compatible with derivatization and analysis. The DFMO derivative (CBI-DFMO) was separated from plasma interferences by multidimensional chromatography with an analysis time of 28 min. The response for DFMO in plasma was linear over the range of 2.1 x 10(-8) 2.1 x 10(-6) M after derivatization. This procedure encompasses a useful linear range and offers the advantages of minimal sample preparation and production of a stable fluorophor.


Perspectives of using fungi as bioresource for bioremediation of pesticides in the environment: a critical review.
Pesticides are used for controlling the development of various pests in agricultural crops worldwide. Despite their agricultural benefits, pesticides are often considered a serious threat to the environment because of their persistent nature and the anomalies they create. Hence removal of such pesticides from the environment is a topic of interest for the researchers nowadays. During the recent years, use of biological resources to degrade or remove pesticides has emerged as a powerful tool for their in situ degradation and remediation. Fungi are among such bioresources that have been widely characterized and applied for biodegradation and bioremediation of pesticides. This review article presents the perspectives of using fungi for biodegradation and bioremediation of pesticides in liquid and soil media. This review clearly indicates that fungal isolates are an effective bioresource to degrade different pesticides including lindane, methamidophos, endosulfan, chlorpyrifos, atrazine, cypermethrin, dieldrin, methyl parathion, heptachlor, etc. However, rate of fungal degradation of pesticides depends on soil moisture content, nutrient availability, pH, temperature, oxygen level, etc. Fungal strains were found to harbor different processes including hydroxylation, demethylation, dechlorination, dioxygenation, esterification, dehydrochlorination, oxidation, etc during the biodegradation of different pesticides having varying functional groups. Moreover, the biodegradation of different pesticides was found to be mediated by involvement of different enzymes including laccase, hydrolase, peroxidase, esterase, dehydrogenase, manganese peroxidase, lignin peroxidase, etc. The recent advances in understanding the fungal biodegradation of pesticides focusing on the processes, pathways, genes/enzymes and factors affecting the biodegradation have also been presented in this review article.


Solubilization of the functional C5a receptor from human polymorphonuclear leukocytes.
The C5a receptor has been extracted in an active state from the membranes of human polymorphonuclear leukocytes with the detergents digitonin and beta-dodecyl maltoside. The solubilized receptor exhibits a single class of high affinity binding sites with a Kd = 90 pM, a value similar to that found with intact membranes. Physical studies with the soluble receptor demonstrate that it exists in two forms which differ in molecular mass. Gel filtration experiments with receptor to which C5a has been bound give an apparent molecular mass for the complex of 150-200 kDa. When the experiments were repeated with nonliganded receptor, most of the C5a binding activity eluted with an apparent mass of 150-200 kDa. However, the peak had a pronounced trailing shoulder indicating that, in the nonliganded state, a portion of the receptor population exists in a smaller form, which may be converted to the larger form on binding C5a. The molecular mass of the smaller form, estimated to be 30-70 kDa, is consistent with that of the binding subunit of the receptor. These data imply that the larger form, and therefore the bulk of the solubilized receptor, is oligomeric, a conclusion which is supported by cross-linking studies. When C5a was cross-linked to the soluble receptor two specific complexes with molecular masses of 52 and 95 kDa were formed. The former is the covalent adduct of C5a and the binding subunit of the receptor and the latter appears to be a complex between the 52-kDa species and an additional polypeptide.


Investigating the role of uric acid and uric acid-to-creatinine ratio as a predictive factor of chronic obstructive pulmonary disease exacerbation in 2019.
Serum uric acid has been suggested as an independent marker of oxidative metabolism in chronic obstructive pulmonary disease (COPD), a disease with significant social, health, and economic burden. Therefore, we aimed to investigate the role of this factor in COPD exacerbation. We investigated 20- to 70-year-old patients who were admitted due to COPD exacerbation (acute phase) or presented to the pulmonary clinic for follow-up (non-acute phase). Correlation of uric acid and uric acid-to-creatinine ratio (UCR) with multiple factors and their predictive performance for more exacerbations and acute phase of COPD was investigated (receiver operating characteristic [ROC] analysis). Overall, 63 patients were enrolled in this study, of whom 79.4% were men. Acute-phase group encompassed 79.4% of the population with a greater rate of heavy smoking and average exacerbation in a year (p-value = 0.009 and <0.001). The mean of uric acid and UCR was 5.6 (SD, 2.35) and 4.4 (SD, 1.9) in the total population, respectively, and were significantly higher in the acute phase and patients with frequent exacerbations (FE ≥ 3 exacerbations a year), p-value <0.05. The area under the curve (AUC) of ROC analysis showed a high performance of uric acid and UCR for predicting acute phase (0.84 [95%CI, 0.73-0.96] and 0.86 [0.74-0.98]), FE (0.72 [0.60-0.85] and 0.75 [0.63-0.87]), and FE among acute-phase patients (AUC, 0.63 [0.46-0.79] and 0.66 [0.50-0.81], respectively). Uric acid and UCR could be invaluable predictors of frequent exacerbation and the acute phase of COPD. Therefore, they might be applicable in evaluating the severity and progress of the disease.


Prognostic stratification of resected pancreatic ductal adenocarcinoma: Past, present, and future.
Pancreatic ductal adenocarcinoma (PDAC) is the digestive cancer with the poorest prognosis, with a 5-year overall survival rate of 7%. Complete surgical resection followed by adjuvant chemotherapy is the only treatment with curative intent. However, many patients with an apparently localized disease who may undergo primary tumor resection already have micro-metastatic disease and will promptly develop metastases. Considering the significant rate of morbidity and mortality upon pancreatic surgery, the pre-operative identification of patients with an aggressive disease is therefore a major clinical issue. Although tumor size, differentiation, margins, and lymph node invasion are the main "classical" prognostic factors, they are not sufficient to fully predict early disease recurrence. In the last decade, multi-omics high-throughput analyses have provided a new insight into PDAC biology and have led to the description of multiple molecular subtypes, with a significant prognostic value for most of them, but that have not yet been transposed to routine clinical practice, mainly due to poor availability of tumor tissue material prior to surgical resection. In this review, we provide an overview of the current status of clinico-pathological and molecular biomarkers (tumor and blood) to predict early recurrence, and their implications for clinical practice and future research development.


Key factors underlying the willingness of patients with cancer to participate in medication redispensing.
Redispensing medication unused by patients to other patients could reduce the environmental burden of medication waste. Simultaneously, associated financial loss could be reduced, particularly for expensive medication such as oral anticancer drugs. An important determinant for successful medication redispensing is patient participation. To identify key factors underlying the willingness of patients with cancer to participate in the redispensing of unused oral anticancer drugs. Semi-structured interviews via telephone or video call were conducted with adult patients diagnosed with cancer from two Dutch hospitals. The interview guide was framed using the COM-B model for behavioural change, to elicit patients' capability, opportunity and motivation to participate in medication redispensing. Questions were related to patients' willingness to accept redispensed medication, reasons thereof, perceived concerns and needs. Inductive thematic analysis was applied. Seventeen patients (aged 38-82 years, 71% female), with nine different types of cancer participated. The majority of participants supported medication redispensing. Four categories of key factors underlying the willingness of patients with cancer to participate in medication redispensing were identified. First, the driver for participation was having positive societal impact, relating to affordability and sustainability of healthcare. Second, having trust in product quality was a requirement, influenced by preconceived beliefs, quality assurance and patients' knowledge of this process. Third, a facilitator for participating in medication redispensing was adequate provision of information. This concerned awareness of medication waste, information about medication redispensing, support from healthcare providers and other patients, and insight into medication dispensing history. Last, a convenient process for returning unused medication to pharmacies would facilitate participation in medication redispensing. The willingness of patients with cancer to participate in medication redispensing relates to a drive for achieving positive societal impact, provided that medication is of high quality, there is adequate information provision and a convenient process.


[Pneumonia in a traveller coming back from Asia].
A case of Salmonella paratyphi A infection was diagnosed late in a patient treated for febrile pneumonia after his returning from India. This case was remarkable in two aspects: first, it illustrated the reemergence of S.paratyphi A infections in people having traveled to India, with increasing fluoroquinolone resistance, and second the difficulty of diagnosing this disease, since the patient was initially treated for pneumonia and flu-like syndrome. Salmonella typhi or paratyphi infections should be evoked in case of persistent fever in patients having traveled to endemic areas, even if digestive signs are absent. Furthermore, choosing an empiric antibiotic treatment with fluoroquinolones could lead to treatment failure if the patient traveled in a country where fluoroquinolone resistance is high, as in Asia and especially in India.


Incidence and risk factors of calcaneal enthesophytes in spondyloarthritis and trauma patients.
Achilles enthesitis and plantar fasciitis are the features of spondyloarthritis (SpA). Enthesophytes may indicate enthesitis, but their incidence is also high in elderly individuals and in athletes. This study aimed to clarify the incidences and risk factors of Achilles enthesophyte (AE) and plantar entesophye (PE) in SpA and trauma patients. We retrospectively surveyed radiographs of the feet of SpA and trauma patients in our hospital. The SpA group included 17 patients (33 feet), and the trauma group included 33 patients (37 feet) who had undergone surgery between April 2013 and March 2014. The incidence of AEs was 63.6% (21 feet) in the SpA group and 54.1% (20 feet) in the trauma group (p = 0.45). The incidence of PEs was 48.9% (16 feet) in the SpA group and 16.2% (6 feet) in the trauma group. The SpA group had a higher prevalence of PEs than the trauma group (p < 0.01). The multivariate analysis showed that the risk factors for AEs and PEs were SpA and age. The risk factors for AEs and PEs were found to be advanced age and the presence of SpA.


Induction of angiogenic tumors in the duodenum of female Donryu rats by continuous oral administration of N-isobutyl-N-nitrosourea.
Four groups of female Donryu rats were continuously given 400, 200, 100 or 0 ppm N-isobutyl-N-nitrosourea (iso-BNU) in their drinking water, and were examined for the development of tumors. The incidence of digestive tract tumors was 25/28 (89%), 14/24 (58%), 6/25 (24%) and 0/17 (0%), in the 400, 200, 100 and 0 ppm groups, respectively. The predominant type of digestive tract tumor was angiogenic, and a few were of the epithelial type. A dose-effect relationship was clearly demonstrated not only in the incidence of digestive tract tumors but also in the average survival period of rats with these tumors.


Perceived HIV stigma and HIV testing among men and women in rural Uganda: a population-based study.
Stigma is a formidable social structural barrier to HIV testing, and yet the effect of stigma on HIV testing is rarely examined at the community level. We aimed to examine the geospatial relationships of perceived HIV stigma and HIV testing among men and women living in rural Uganda. Women and men (aged ≥18 years or emancipated minor) residing in rural areas of Uganda who self-identified as HIV negative completed interviews that included measures of HIV testing history and how participants perceived HIV stigma. We used geospatial cluster analyses to identify areas of higher perceived stigma and lower perceived stigma and the geographical dispersion of these areas. We used Poisson regression models stratified by gender to test individual-level and community-level perceived stigma in relation to frequency of HIV testing in the previous 2 years. Between Nov 25, 2015, and May 26, 2017, we interviewed 9740 participants (4359 [45%] men and 5381 [55%] women]), among whom 940 (9%) had never been tested for HIV, and among those who had been tested, 1131 (12%) had not been tested in the previous 2 years. Men (3134 [72%] of 4359) were less likely to have been tested in the past 2 years than women (4535 [84%] of 5381) were (p<0·001). We used Poisson regression models, reporting B coefficients, to test study hypotheses regarding the effects of individual-level and community-level stigma on HIV testing frequency counts. Multilevel modelling showed that women showed significant individual-level (B=-0·173, p<0·001) and community-level (B=-0·223, p<0·001) associations between lower stigma predicting higher rates of HIV testing. For men, lower individual-level perceived stigma was also associated with higher testing frequency (B=-0·030, p=0·018), whereas higher community-level perceived stigma was associated with higher testing frequency (B=0·077, p=0·008). Our results suggest that perceived HIV stigma at the community level exerts a differential influence on testing for women and men. HIV testing campaigns that are targeted to men and women in rural Uganda will require gender tailoring to fit local contexts. US National Institute of Mental Health.


Head and neck findings in pediatric acquired immune deficiency syndrome.
Since the initial reports of an immune deficiency syndrome affecting certain segments of the adult population (homosexual males, bisexual males, intravenous drug abusers, prostitutes, hemophiliacs, Haitian immigrants), a specific group of pediatric patients with an identical immunologic picture has been identified. This report describes the head and neck findings seen in a group of these pediatric patients. Ninety percent were microsomic. Developmental delay occurred in 90%. Inflammatory ear disease occurred in 80%. Lymphocytic interstitial pneumonia and mucocutaneous candidiasis each occurred in 80%, cortical atrophy in 60%, cervical adenopathy in 40%, and parotid enlargement in 30%. The otolaryngologist may be called upon to evaluate patients with pediatric acquired immune deficiency syndrome (PAIDS), and therefore, should be familiar with the head and neck manifestations of this disease.


A flat capillary tube system for assessment of sperm movement in cervical mucus.
A new flat capillary tube system has been developed for studies of sperm movement in cervical mucus. The system is easy to use, employs readily obtainable components, and is amenable to small sample sizes characteristic of human cervical mucus. The system possesses good optical resolution and is suitable for visual assessment of sperm migration as well as more detailed studies of the movement characteristics of individual spermatozoa. The system subjects the mucus to a well-defined and controllable rate of shear deformation. Preliminary experiments have suggested that the swimmming speed of human sperm does not differ in flat capillary tubes of 200-micrometer and 400-micrometer depth.


Reduced graphene oxide-based field effect transistors for the detection of E7 protein of human papillomavirus in saliva.
Several challenging biological sensing concepts have been realized using electrolyte-gated reduced graphene oxide field effect transistors (rGO-FETs). In this work, we demonstrate the interest of rGO-FET for the sensing of human papillomavirus (HPV), one of the most common sexually transmitted viruses and a necessary factor for cervical carcinogenesis. The highly sensitive and selective detection of the HPV-16 E7 protein relies on the attractive semiconducting characteristics of pyrene-modified rGO functionalized with RNA aptamer Sc5-c3. The aptamer-functionalized rGO-FET allows for monitoring the aptamer-HPV-16 E7 protein binding in real time with a detection limit of about 100 pg mL-1 (1.75 nM) for HPV-16 E7 from five blank noise signals (95% confidence level). The feasibility of this method for clinical application in point-of-care technology is evaluated using HPV-16 E7 protein suspended in saliva and demonstrates the successful fabrication of a promising field effect transistor biosensor for HPV diagnosis.Graphical abstract.


Constructing Biomimetic Cardiac Tissues: A Review of Scaffold Materials for Engineering Cardiac Patches.
Engineered cardiac patches (ECPs) hold great promise to repair ischemia-induced damages to the myocardium. Recent studies have provided robust technological advances in obtaining pure cardiac cell populations as well as various novel scaffold materials to generate engineered cardiac tissues that can significantly improve electrical and contractile functions of damaged myocardium. Given the significance in understanding the cellular and extracellular structural as well as compositional details of native human heart wall, in order to fabricate most suitable scaffold material for cardiac patches, herein, we have reviewed the structure of the human pericardium and heart wall as well as the compositional details of cardiac extracellular matrix (ECM). Moreover, several strategies to obtain cardiac-specific scaffold materials have been reviewed, including natural, synthetic and hybrid hydrogels, electrospun fibers, decellularized native tissues or whole organs, and scaffolds derived from engineered cell sheets. This review provides a comprehensive analysis of different scaffold materials for engineering cardiac tissues.


A novel classification of HCC basing on fatty-acid-associated lncRNA.
Aberrant long noncoding RNA (lncRNA) expression and fatty acid signaling dysfunction both contribute to hepatocellular carcinoma (HCC) occurrence and development. However, the relationship and interaction mechanism between lncRNAs and fatty acid signaling in HCC remain unclear. Data regarding RNA expression and clinical outcomes for patients with HCC were obtained from The Cancer Genome Atlas (TCGA), HCCDB, and the Gene Expression Omnibus (GEO) databases. Hallmark pathways were identified using the single-sample gene set enrichment analysis (ssGSEA) method. ConsensusClusterPlus was used to establish a consistency matrix for classifying samples into three subtypes. A risk signature was established, and predictive values for key lncRNAs related to prognosis were evaluated using Kaplan-Meier analysis and receiver operating characteristic curves. The ESTIMATE algorithm, MCP-Counter, and ssGSEA were used to evaluate the characteristics of the tumor immune microenvironment. The CTRP2.0 and PRISM were used to analyze drug sensitivity in HCC subtypes. We discovered seven fatty-acid-associated lncRNAs with predictive prognostic capabilities, including TRAF3IP2-AS1, SNHG10, AL157392.2, LINC02641, AL357079.1, AC046134.2, and A1BG-AS. Three subtypes were obtained, which presented with differences in prognosis, clinical information, mutation features, pathway traits, immune characteristics, and drug sensitivity. The seven key lncRNAs identified in this study might serve as promising biomarkers for predicting prognosis in patients with HCC, and the three HCC subtypes classified according to lncRNA expression profiles could improve HCC classification.


Understanding current steam sterilization recommendations and guidelines.
Processing surgical instruments in preparation for surgery is a complex multistep practice. It is impractical to culture each and every item to determine sterility; therefore, the best assurance of a sterile product is careful execution of every step in the process coupled with an ongoing quality control program. Perioperative staff nurses and managers responsible for instrument processing, whether for a single instrument or multiple sets, must be knowledgeable with regard to cleaning; packaging; cycle selection; and the use of physical, chemical, and biological monitors. Nurses also should be able to resolve issues related to loaner sets, flash sterilization, and extended cycles.


Fungal Epithiodiketopiperazines Carrying α,β-Polysulfide Bridges from Penicillium steckii YE, and Their Chemical Interconversion.
Some fungal epithiodiketopiperazine alkaloids display α,β-polysulfide bridges alongside diverse structural variations. However, the logic of their chemical diversity has rarely been explored. Here, we report the identification of three new (2, 3, 8) and five known (1, 4-7) epithiodiketopiperazines of this subtype from a marine-derived Penicillium sp. The structure elucidation was supported by multiple spectroscopic analyses. Importantly, we observed multiple nonenzymatic interconversions of these analogues in aqueous solutions and organic solvents. Furthermore, the same biosynthetic origin of these compounds was supported by one mined gene cluster. The dominant analogue (1) demonstrated selective cytotoxicity to androgen-sensitive prostate cancer cells and HIF-depleted colorectal cells and mild antiaging activities, linking the bioactivity to oxidative stress. These results provide crucial insight into the formation of fungal epithiodiketopiperazines through chemical interconversions.


The diagnostic efficacy of magnetic resonance imaging and ultrasonography in Morton's neuroma: a radiological-surgical correlation.
All patients operated upon for Morton's neuroma during 1991 who were examined with both magnetic resonance imaging and ultrasonography were included in this prospective study. The object of the study was to evaluate the diagnostic value of these two modalities. The preoperative diagnosis was purely clinical. Histology confirmed surgical findings. A 0.3 T scanner was used for the magnetic resonance imaging, and a 7.5 MHz linear transducer was used for the ultrasonography. The study includes nine patients. Eight neuromas were found at surgery. Of these, only five were diagnosed with magnetic resonance imaging and three with ultrasonography. This indicates that false negative diagnoses are common. At present we find these modalities of little or no value, but, with improved equipment and experience, they may become valuable.


Optimization of in-pipe storage capacity use in urban drainage systems with improved DP considering the time lag of flow routing.
The active control of urban drainage systems (UDSs) is playing an increasingly important role in the world threatened by urban flooding and associated disasters caused by insufficient drainage capacity. However, little research has recognized the importance of the optimal use of in-pipe storage space. To address this issue, the use of the in-pipe storage capacity was optimized in this study. A novel approach, that is, dynamic programming with successive approximation considering the time lag of flow routing (DPSA-TL), was developed to determine the control policies, in addition to the commonly used passive, rule-based control (RBC), and evolutionary algorithm (EA) strategies. A real-life urban catchment considering flooding control and combined sewer overflow (CSO) reduction was used as the case study. First of all, the potential benefit of maximizing the use of in-pipe storage space was tested using the four control strategies in three storm events, including a 3-year, 2-hour design (46.5 mm), a 5-year, 2-hour design (56.0 mm) and a 7-h historical (152.5 mm) storm events. Results indicate that DPSA-TL performed best in all cases. Without compromising the goal of flooding control, it provided 16.5%, 12.6%, and 3.0% reductions in CSO volume for the three storm events when compared with the passive strategy. Due to the limited capacity of in-pipe storage, the relative improvement diminished as the total rainfall depth increased. Then, control strategies were further applicated to the real-time operation. DPSA-TL was found to be the best alternative for CSO control, with the CSO volume reduced by 14.7%, 11.4%, and 2.5% in the three storm events, respectively. The findings suggest that the performance of UDS can be significantly improved by optimizing the use of in-pipe storage capacity, and the proposed method is effective in the offline optimization and real-time control of UDSs.


Intraprostatic fiducials for localization of the prostate gland: monitoring intermarker distances during radiation therapy to test for marker stability.
The use of intraprostatic fiducials as surrogates for prostate gland position assumes that the markers are rigidly positioned within the prostate. To test this assumption, the intermarker distances (IMD) of implanted markers was monitored during the full course of radiation therapy to determine marker stability within the prostate gland. The analysis is performed on 56 patients treated with intensity-modulated radiotherapy. A total of 168 markers (3 markers per patient) were implanted. Two high-resolution X-rays were acquired before treatment delivery to visualize the position of the implanted markers. A total of 2,037 daily alignments were performed on the 56 cases (average: 36 alignments per patient). Each pair of X-ray images allows the computation of the 3 IMDs. A total of 6,111 IMDs were available for analysis. To study variations in marker position, daily IMDs were compared with the IMD that was observed during the first alignment. We defined the variation in the IMD as the important measure of intrinsic marker position variation. The standard deviation (SD) of IMD variations was studied as a measure of the extent of marker position variation. Particular attention was given to cases in which significant intermarker variations were observed. The average directional variation of all IMDs (+/- SD) was -0.31 (+/-1.41) mm. The average absolute variation of all IMDs (+/- SD) was 1.01 (+/-1.03) mm. The largest observed variation in IMD was 10.2 mm. Among the individual 56 patients, the SDs of the IMD variations were computed and found to range from 0.4 to 4.2 mm. In 54 of the 56 patients (96%), the variations of all 3 IMDs had SD of 4.0 mm or less, which indicates little variation in the relative position of the markers. Only in 2 patients did any of the IMDs vary, with SD that exceeded 4.0 mm, which indicated noticeable and consistent marker-position variation. The maximum observed SD in the IMD variation was 4.2 mm. In each of the 2 cases, 2 IMDs were found to fluctuate, while the third IMD remained fairly constant. This finding means that 1 of 3 markers varied frequently in its relative position throughout the treatment. Therefore, only 2 of the 168 markers (1%) showed frequent changes in their relative positions. A review of these 2 cases revealed that the observed marker mobility was likely not caused by migration of the marker itself but caused by prostate deformation, secondary to rectal filling. To investigate the frequency of extreme situations, the maximum observed IMD variation was determined for each patient. In 47 of the 56 patients (84%), the maximum difference in IMDs was at least 2 mm. The corresponding numbers for 3, 4, and 5 mm were 23 (41%), 10 (18%), and 5 (9%) patients, respectively. This study is the largest reported series of localized prostate cancer patients with implanted intraprostatic markers used for daily target localization in which individual marker positions were registered and IMDs were computed to test for marker position variation. Only 2 of 168 implanted markers showed a relatively significant and consistent change in their relative position throughout a course of treatment. However, these variations in position were most likely not caused by marker migration but caused by prostate deformation. Typically, the IMDs varied minimally, which indicated relatively little deformation of the gland as well as the absence of significant marker migration. However, during a typical course of treatment, the IMD is likely to vary by several millimeters in some instances, which indicates infrequent but significant deformation. In these instances, an alignment based on the 3 markers' center of mass will still provide a meaningful alignment of the prostate within the radiation field. Intraprostatic implanted fiducials in the prostate allow a reliable and simple localization of the prostate gland, even in the presence of organ deformation.


Effects of Xylitol and CPP-ACP Chewing Gum on Salivary Properties of Children with Molar Incisor Hypomineralization.
To compare the efficacy of chewing gum containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and xylitol on salivary characteristics in 8-10 years old children with molar incisor hypomineralization. A randomized controlled trial using CPP-ACP chewing gums (group I) and xylitol chewing gums (group II) was conducted among 32 children affected with mild molarincisor hypomineralization (MIH). Salivary flow rate, pH and buffering capacity were measured using saliva check kit (GC America). Data obtained were tabulated and subjected to statistical analysis using SPSS software version 20. Descriptive statistics-mean, standard deviation, 95% confidence interval. Inferential statistics-independent t tests were used. A significant increase in mean salivary pH, flow rate and buffering action was observed from baseline to immediately after spitting the chewing gum in both the study groups (p 0.05). Casein phosphopeptide-amorphous calcium phosphate containing chewing gums improve salivary characteristics in MIH-affected children. Xylitol and CPP-ACP chewing gums are recommended in MIH children with early demarcated opacities as it improves the salivary properties in those children and prevents further complications. Prathima GS, Narmatha M, Selvabalaji A, et al. Effects of Xylitol and CPP-ACP Chewing Gum on Salivary Properties of Children with Molar Incisor Hypomineralization. Int J Clin Pediatr Dent 2021;14(3):412-415.


A cold active (2R,3R)-(-)-di-O-benzoyl-tartrate hydrolyzing esterase from Rhodotorula mucilaginosa.
In a screening procedure a pink-colored yeast was isolated from enrichment cultures with (2R,3R)-(-)-di-O-benzoyl-tartrate (benzoyl-tartrate) as the sole carbon source. The organism saar1 was identified by morphological, physiological, and 18S ribosomal DNA/internal transcribed spacer analysis as Rhodotorula mucilaginosa, a basidiomycetous yeast. During growth the yeast hydrolyzed the dibenzoyl ester stoichiometrically to the monoester using the separated benzoate as the growth substrate, before the monoester was further cleaved into benzoate and tartrate, which were both metabolized. The corresponding benzoyl esterase was purified from the culture supernatant and characterized as a monomeric glycosylated 86-kDa protein with an optimum pH of 7.5 and an optimum temperature of 45 degrees C. At 0 degrees C the esterase still exhibited 20% of the corresponding activity at 30 degrees C, which correlates it to psychrophilic enzymes. The esterase could hydrolyze short chain p-nitrophenyl-alkyl esters and several benzoyl esters like benzoyl-methyl ester, ethylene-glycol-dibenzoyl ester, phenyl-benzoyl ester, cocaine, and 1,5-anhydro-D: -fructose-tribenzoyl ester. However feruloyl-ethyl ester was not hydrolyzed. The activity characteristics let the enzyme appear as a promising tool for synthesis of benzoylated compounds for pharmaceutical, cosmetic, or fine chemical applications, even at low temperatures.


Endovascular treatment of iatrogenic iliac artery disruption in lumbar disc surgery.
Major vessel (aorta or iliac vessels) injury is a rare yet catastrophic complication of spinal surgery. Prompt diagnosis is vital for effectively treating these injuries. A 56-year-old female with iliac artery iatrogenic injury during lumbar discectomy was successfully treated by percutaneous placement of a self-expanding stent graft in an emergent setting in an angiography suite. Postprocedural angiogram demonstrated complete exclusion of the pseudoaneurysm without contrast agent leakage. Endovascular treatment is suggested as an excellent alternative to open surgery for iatrogenic great vessel injuries, particularly in critical conditions.


Novel computational models for predicting dopamine interactions.
Dopamine is a crucial neurotransmitter responsible for functioning and maintenance of the nervous system. Dopamine has also been implicated in a number of diseases including schizophrenia, Parkinson's disease and drug addiction. Dopamine agonists are used in early Parkinson's disease treatment. Dopamine antagonists suppress schizophrenia. Therefore, molecules modulating dopamine receptors activity are vastly important for understanding the nervous system functioning and for the treatment of neurological diseases. In this study we describe novel computational models that efficiently predict binding affinity of the existing small molecule dopamine analogs to dopamine receptor. The model provides the set of molecular descriptors that can be used for the development of new small molecule dopamine agonists.


Morpheaform basal cell carcinoma of the nasal ala associated with multiple familial trichoepithelioma reconstructed by anterolateral thigh flap: a case report.
The right nasal ala had been destroyed and was diagnosed as morpheaform basal cell carcinoma associated with multiple familial trichoepithelioma (Brooke-Spiegler syndrome). After extended resection, the right buccal and nasal ala defect was reconstructed with a flow-through type anterolateral thigh (ALT) flap, which achieved good functional and cosmetic results.


Research Techniques Made Simple: Molecular Docking in Dermatology - A Foray into In Silico Drug Discovery.
Drug discovery is a complex process with many potential pitfalls. To go to market, a drug must undergo extensive preclinical optimization followed by clinical trials to establish its efficacy and minimize toxicity and adverse events. The process can take 10-15 years and command vast research and development resources costing over $1 billion. The success rates for new drug approvals in the United States are < 15%, and investment costs often cannot be recouped. With the increasing availability of large public datasets (big data) and computational capabilities, data science is quickly becoming a key component of the drug discovery pipeline. One such computational method, large-scale molecular modeling, is critical in the preclinical hit and lead identification process. Molecular modeling involves the study of the chemical structure of a drug and how it interacts with a potential disease-relevant target, as well as predicting its ADMET properties. The scope of molecular modeling is wide and complex. Here we specifically discuss docking, a tool commonly employed for studying drug-target interactions. Docking allows for the systematic exploration of how a drug interacts at a protein binding site and allows for the rank-ordering of drug libraries for prioritization in subsequent studies. This process can be efficiently used to virtually screen libraries containing over millions of compounds.


Testis sparing surgery for steroid unresponsive testicular tumors of the congenital adrenal hyperplasia.
The association between testicular tumors/nodules and congenital adrenal hyperplasia (CAH) has been recognized for many years. Tumors are considered to be an aberrant adrenal tissue that has descended with the testes and has become hyperplastic due to ACTH stimulation. The recommended treatment consists of increasing the glucocorticoid dose to suppress ACTH secretions. If the testicular size is not reduced after suppression therapy or a side effect of glucocorticoid dose is noted, surgical intervention should be considered. We diagnosed steroid unresponsive testicular tumors of the CAH in two patients who were treated by testicular sparing tumor enucleation. We believe that testis sparing surgery is the procedure of choice for all patients with testicular adrenal rest tumor, since it maximizes future fertility potential.


Foraging strategies and recruitment behaviour in the European harvester ant Messor rufitarsis (F.).
Most of the approximately 40 species of the Old World harvester ant genus Messor live in warm and dry Mediterranean areas. One species, M. rufitarsis, is found in isolated Northern temperate habitats in Rheinhessen and the Rheingau area in Hessen, West Germany. These habitats are characterized by a great diversity of spermatophytes, so that permanently changing seed resources are available for the ants during the growing period. M. rufitarsis has maintained its granivorous specialization under these habitat conditions and collects most of the seed resources, which show a large fluctuation in quantity, quality and distributional pattern throughout the year. M. rufitarsis is very flexible in using different foraging strategies. For discovering newly ripened food resources and collecting wide-spread single seeds, an individual foraging strategy is used. However, dense seed resources are exploited through an effective recruitment system. Nestmates are guided to the feeding place by means of orientation-recruitment trails from Dufour's gland. Additional invitation behaviour enhances the success of recruitment. From analysis of slow-motion movies it is concluded that stridulation is the crucial signal of the invitation behaviour.


Heterotopic gastric mucosa of the duodenum mimicking a duodenal cancer.
Heterotopic gastric mucosa of peculiar shape and located in the duodenum bore a close resemblance to superficial ulcerating cancer. Radiographic survey showed a flexible lesion with a mucosal pattern resembling area gastrica. Endoscopy revealed its color to be indistinguishable from that of the normal duodenal mucosa. These may be characteristic features of this abnormality.


[Dose-effect relations. Doubleblind study on two different doses of pimozide (author's transl)].
Two identical groups of schizophrenic patients were treated for 28 days randomized with 3 and 8 mg of pimozide. In the antipsychotic efficacy no difference could be seen. Difference was in side effects: The 8-mg group had three times more extrapyramidal signs, mostly akathisia and agitation, and needed seven times more minor tranquilizer than the 3-mg group. Severe agitation as a psychotic symptom was equal in both groups. Preference therefore is given to the smaller dosage.


Simultaneous determination of pantothenic acid and hopantenic acid in biological samples and natural products by gas chromatography-mass fragmentography.
A method for the simultaneous determination of pantothenic acid and hopantenic acid in plasma samples was developed using gas chromatography-mass spectrometry with multiple ion detection. Plasma samples were directly purified without deproteinization on an ion-exchange resin, and the eluate was extracted with ethyl acetate under acidic conditions. The organic layer was evaporated to dryness under a stream of nitrogen, and the residue was dissolved in an internal standard solution. Pantothenic and hopantenic acids were converted into their trimethylsilyl derivatives by treating with bis(trimethylsilyl)trifluoroacetamide. Aliquots of this solution were injected into the gas chromatograph-mass spectrometer, which was equipped with a wide-bore fused-silica column (DB-17) and analysed by the multiple ion detection method. The detection limits for pantothenic acid and hopantenic acid in plasma were 1 ng/ml each at a signal-to-noise ratio of 5. This method was applied to a study of the assay of pantothenic acid and hopantenic acid in biological samples and natural products.


Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area.
Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT(2) receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT(2) receptor activation can influence sexual differentiation of the brain by controlling AR expression.


Human amniotic epithelial cell niche enhances the functional properties of human corneal endothelial cells via inhibiting P53-survivin-mitochondria axis.
The particular microenvironment or niche plays an important role in determining the fate of stem cells and adult cells. The objective of this study was to explore the potential role of the niche of human amniotic epithelial cells in enhancing the functional properties of human corneal endothelial cells (HCECs). The HCECs were cultured in different media, including corneal endothelium medium (CEM), 20% human amniotic epithelial cell culture medium (20% HAEC-Me), and 20% human amniotic epithelial cell-conditioned medium (20% HAEC-CM). We observed that the HCECs cultured in the 20% HAEC-CM had an increased proliferative capacity, higher colony-forming efficiency (CFE), fewer apoptotic cells, and similar cell-junction formation capabilities and pump functionality compared with primary HCECs. Compared with CEM and 20% HAEC-Me, the 20% HAEC-CM system enhanced the functional properties of HCECs by reducing the generation of reactive oxygen species (ROS), maintaining the membrane potential (Δψm) at higher levels, reducing the expression of the p53 protein, and increasing the level of survivin protein expression. This study may shed light on the expansion of HCECs and the clinical applications of these cells in regenerative medicine, especially in corneal tissue engineering.


[Glucagon-like peptide-1 protects INS-1 cells from interleukin-1β-induced damage by inhibiting the nuclear factor-κB pathway.].
To observe the effect of glucagon-like peptide-1 (GLP-1) on interleukin-1β (IL-1β)-induced damage in INS-1 cells and explore its possible mechanisms. INS-1 cells were divided into normal control group, IL-1β group, and GLP-1+IL-1β group with corresponding treatments. The cell viability was determined by MTT assay, the expression of IKKβ mRNA was detected by real-time PCR, and that of the protein p65 was detected by Western blotting. In comparison with the normal control group, the cells in the IL-1β group showed a significantly decreased viability by 29% (P < 0.01); compared with those in IL-1β group, the cells in GLP-1+IL-1β group exhibited an significant increase in the cell viability by 30% (P < 0.01). In comparison with the normal control group, the cells in IL-1β group showed an significantly increased expression of IKKβ mRNA (1.967 ± 0.091 vs 1 ± 0, P < 0.05); GLP-1 significantly reduced IL-1β-induced increment of IKKβ mRNA expression to 1.287 ± 0.084 (P < 0.05). IL-1β treatment significantly increased NF-κB protein expression as compared to the control level (0.814 ± 0.111 vs 0.396 ± 0.026, P < 0.01), and GLP-1 significantly inhibited such effect (0.622 ± 0.059, P < 0.05). GLP-1 inhibits IL-1β-induced β-cell damage probably by inhibiting the NF-κB pathway.


New website offers wider content for readers on the go.
NURSING CHILDREN and Young People is launching a new website designed to give our readers a better experience when using the journal online.


Influence of food on bioavailability from two controlled-release granules of theophylline.
The bioavailability and absorption pattern of theophylline from Theolong granule and Theodur-G were studied in five healthy volunteers both in fasting conditions and after taking two different meals. In all the subjects, no dose-dumping effect was observed with a standard- or a fat-rich breakfast on these preparations. Postprandial administration delayed the absorption of theophylline and a fat-rich breakfast significantly reduced the area under the curve (AUC0-26) for both preparations. The mean AUC decreased by 14.0% for the former and 19.7% for the latter when the fat-rich breakfast was administered. Intake of a standard breakfast resulted in a decrease in the AUC0-26 by 10.6% for Theolong granules but there was little effect observed with the Theodur-G granules.


Further examination of the cross-country association between income inequality and population health.
Several scholars have put forward the view that the estimates by Rodgers [(1979). Income and inequality as determinants of mortality: An international cross-section analysis. Population Studies, 33 (2), 343-351], Flegg [(1982). Inequality of income, illiteracy and medical care as determinants of infant mortality in underdeveloped countries. Population Studies, 36 (3), 441-458] and Waldmann [(1992). Income distribution and infant mortality. Quarterly Journal of Economics, 107 (4), 1283-1302] showing a negative cross-country association between income inequality and population health, cannot be replicated from recent data. In view of the importance of this matter, the present study further examines the issue from the most recent, and probably more accurate, data for the largest cross-country sample used in this line of research. The main conclusion is that the negative cross-country association between income inequality and good health, reported by Rodgers, Flegg, and Waldmann, is replicated very well. The different findings indicated by some scholars may have been due to their samples or the models being unusual. Therefore, the recent skepticism about the existence of such a negative association needs to be reconsidered. Several additional points are also noted. First, income inequality shows significance even after an index of ethnic heterogeneity is included. Second, ethnic heterogeneity itself has a negative association with population health. Third, income inequality retains significance in the presence of a measure of social capital. Fourth, however, the association between the measure of social capital and population health appears weak. Fifth, a simple analysis does not support the view that the positive association between income inequality and infant mortality in less developed countries (LDCs) may just be a reflection of the role of poverty. Finally, there is some support for the proposition that while income may be relatively more important for health in LDCs, the role of income inequality may be stronger in developed economies.


Trust, health, and longevity.
Scores on the Rotter Interpersonal Trust Scale were evaluated as predictors of psychological well-being, functional health, and longevity in a sample of 100 men and women who were between 55 and 80 years old at baseline (mean age 66.8). Cross-sectionally, high levels of trust were associated with better self-rated health and more life satisfaction. Follow-up over approximately 8 years found baseline levels of trust to be positively related to subsequent functional health, but not to subsequent life satisfaction. Mortality follow-up after 14 years demonstrated that those with high levels of trust had longer survival (p = .03), a finding that was somewhat weakened by controlling for baseline health ratings. These findings illustrate the health protective effects of high levels of trust and suggest the potential usefulness of the trust concept for understanding successful aging.


Enhanced production of laccase from Coriolus versicolor NCIM 996 by nutrient optimization using response surface methodology.
Plackett and Burman design criterion and central composite design were applied successfully for enhanced production of laccase by Coriolus versicolor NCIM 996 for the first time. Plackett and Burman design criterion was applied to screen the significance of ten nutrients on laccase production by C. versicolor NCIM 996. Out of the ten nutrients tested, starch, yeast extract, MnSO(4), MgSO(4) x 7H(2)O, and phenol were found to have significant effect on laccase production. A central composite design was applied to determine the optimum concentrations of the significant variables obtained from Plackett-Burman design. The optimized medium composition for production of laccase was (g/l): starch, 30.0; yeast extract, 4.53; MnSO(4), 0.002; MgSO(4) x 7H(2)O, 0.755; and phenol, 0.026, and the optimum laccase production was 6,590.26 (U/l), which was 7.6 times greater than the control.


[Surgical costs in an otorhinolaryngology department].
To describe the costs of the surgical procedures most frequently performed in an Otorhinolaryngology Department. A descriptive economic analysis of the 5 most frequent surgical procedures performed during 2006, based on the following variables: human resources, non-structural equipment, medication, diagnostic tests and hospitalization during pre-operative, intra-operative, and post-operative phases. Of the 1108 procedures, the most common was tonsillectomy/adenoidectomy with 25.45 % (282), followed by thyroidectomy/hemithyroidectomy with 8.39 % (93), septoplasty with 8.3 % (92), endoscopic CO2 laser with 8.21 % (91) and tympanoplasty with 7.85 % (87). The total cost for each surgical procedure was 301.02 euro, 1422.09 euro, 315.57 euro, 1245.29 euro, and 1454.04 euro, respectively. The analysis of costs shows a direct relationship between the complexity of the procedure and its cost, in terms of human resources, equipment and hospitalization. The use of ambulatory surgery units positively influenced by reducing costs.


Myeloperoxidase acts as a source of free iron during steady-state catalysis by a feedback inhibitory pathway.
Myeloperoxidase (MPO) is a heme-containing enzyme that generates hypochlorous acid (HOCl) from chloride (Cl(-)) and hydrogen peroxide (H₂O₂). It is implicated in the pathology of several chronic inflammatory conditions such as cardiovascular and pulmonary diseases and cancer. Recently we have shown that HOCl can destroy the heme prosthetic group of hemoproteins. Here, we investigated whether the HOCl formed during steady-state catalysis is able to destroy the MPO heme moiety and thereby function as a major source of free iron. UV-visible spectra and H₂O₂-specific electrode measurements recorded during steady-state HOCl synthesis by MPO showed that the degree of MPO heme destruction increased after multiple additions of H₂O₂ (10 µM), precluding the enzyme from functioning at maximum activity (80-90% inhibition). MPO heme destruction occurred only in the presence of Cl(-). Stopped-flow measurements revealed that the HOCl-mediated MPO heme destruction was complex and occurred through transient ferric species whose formation and decay kinetics indicated it participates in heme destruction along with subsequent free iron release. MPO heme depletion was confirmed by the buildup of free iron utilizing the ferrozine assay. Hypochlorous acid, once generated, first equilibrates in the solution as a whole before binding to the heme iron and initiating heme destruction. Eliminating HOCl from the MPO milieu by scavenging HOCl, destabilizing the MPO-Compound I-Cl complex that could be formed during catalysis, and/or inhibiting MPO catalytic activity partially or completely protects MPO from HOCl insults. Collectively, this study elucidates the bidirectional relationship between MPO and HOCl, which highlights the potential role of MPO as a source of free iron.


Malaria diagnostic and treatment practices for febrile children under 5 years at two general hospitals in Karamoja, a high transmission setting in Uganda.
Malaria is one of the leading causes of morbidity and mortality among children under 5 years of age in Uganda. Although Karamoja sub-region has the highest prevalence of malaria, and one of the highest case fatality rates in children under 5 years, information on malaria case management for the sub-region is scarce. The study evaluated the malaria diagnostic and treatment practices, as well as the factors associated with inappropriate care for children under 5 years of age presenting with fever in two public hospitals within the sub-region. A cross-sectional study was conducted amongst 857 children under 5 years of age who presented with fever at Abim and Kaabong general hospitals between February and March 2020. A questionnaire was administered to the primary caregiver during exit/bedside interviews to collect socio-demographic information. The participant clinical notes were reviewed to capture information on laboratory tests conducted, diagnosis given, and treatment prescribed. In addition, a health facility assessment was conducted and information on healthcare workers was collected. The healthcare worker and facility data was linked to the participant's hospital visit. Main outcome measures were malaria diagnostic and treatment practices. Of the 857 children enrolled, 820 (95.7%) had a malaria diagnostic test done and 623 (76.0%) tested positive for malaria. All test positive children received anti-malarial treatment, however, only 424/623 (68.1%) received the recommended anti-malarial drug and 376/424 (88.7%) received the right dose of the treatment. Inappropriate diagnosis/treatment was in 321 (37.5%) of the enrolled participants. Factors associated with inappropriate diagnosis/treatment included: lack of recommended anti-malarials on the day of the visit (Prevalence Ratio [PR] = 2.1, 95% confidence interval [CI] 1.8-2.4), hospital where care was sought (PR = 0.4, 95% CI 0.3-0.5), being managed by a recently supervised health worker (PR = 0.5, 95% CI 0.2-0.9), and health worker cadre (PR = 0.8, 95% CI 0.7-0.9). The prevalence of inappropriate malaria diagnosis and treatment in the Karamoja sub-region was high with approximately one in every three children receiving inappropriate care. This was majorly influenced by health system factors, which if improved upon may reduce malaria-related mortalities in the sub-region a vital step in meeting the country's target of zero deaths from malaria by 2030.


Use of nifedipine to decrease ischemic-reperfusion injury in the surgical setting.
This report summarizes studies that provided a basis for a randomized clinical trial of nifedipine in cold hyperkalemic cardioplegic solution. Data from normothermic, isolated working rabbit heart studies demonstrated that presence of micromolar concentrations of nifedipine in the perfusate during continuous low flow or nifedipine used as bolus washouts during global ischemia prevented increases in systolic and diastolic stiffness, which could be related to dose and prevention of intracellular accumulation of calcium. Other studies in open-chest dogs in whom regional ischemia was produced showed that nifedipine was superior to sodium nitroprusside when infused during the ischemic and reperfusion intervals with respect to preservation of hemodynamic variables and reduction of myocardial injury. Further, data from cardiopulmonary bypass experiments in dogs conducted at myocardial temperatures of 37, 28, 18 and 12 degrees C with 1, 2 and 3 hours of global ischemia all demonstrated significant efficacy. To date, the randomized clinical trial has shown a small reduction in the incidence of low cardiac output syndrome in high-risk patients. Those receiving nifedipine had improved hemodynamic variables. No patient in the treated group had myocardial injury in the postoperative interval shown by radionuclide pyrophosphate scan. The conclusions from this trial are that nifedipine was efficacious when included in a cold hyperkalemic cardioplegic solution. The responses observed, however, appear to be dose-, vehicle- and species-dependent.


Youth E-Cigarette Initiation After the Food and Drug Administration's Missed Deadline.
The U.S. Food and Drug Administration was ordered to evaluate electronic nicotine delivery system (ENDS) products by September 9, 2021, but missed the court-ordered deadline. This study provides an estimate of electronic cigarette (E-cigarette) use initiation among youth and young adults after the U.S. Food and Drug Administration's missed deadline. Data were obtained from the Truth Longitudinal Cohort, a probability-based longitudinal sample of youth and young adults aged between 15 and 24 years (N=1,393). Respondents were surveyed at baseline (July-October 2021) and at follow-up (January-June 2022). Individuals who had not previously used any E-cigarette products were included in analyses conducted in 2022. Results indicate that 6.9% of youth and young adults had initiated E-cigarette use, suggesting that about 900,000 youth aged 15-17 years and 320,000 young adults aged 18-20 years initiated E-cigarette use after the U.S. Food and Drug Administration's missed court-ordered deadline. Over a million youth and young adults initiated E-cigarette use after the U.S. Food and Drug Administration's missed court-ordered deadline. The U.S. Food and Drug Administration needs to continue evaluating premarket tobacco product applications, enforce decisions on premarket tobacco product applications, and remove E-cigarettes that are deemed harmful to public health to effectively address the E-cigarette epidemic among young people.


A Phase I Study of the Hsp90 Inhibitor AUY922 plus Capecitabine for the Treatment of Patients with Advanced Solid Tumors.
This phase I study determined the maximum tolerated dose (MTD) of AUY922 with capecitabine in advanced solid tumors. Capecitabine 1000 mg/m(2) PO BID was administered with escalating doses of AUY922 IV; the MTD of AUY922 was combined with capecitabine 1250 mg/m(2) (DL6). 23 patients were treated at 5 dose levels (22 mg/m(2)-70 mg/m(2)). No DLTs were observed until DL6 (grade 3 diarrhea). Reversible vision darkening was seen in 26%. Four patients had partial response; 2 previously progressed on fluorouracil. Eight patients had stable disease (median 25.5 weeks). AUY922 plus capecitabine was well-tolerated up to 70 mg/m(2) with encouraging preliminary efficacy.


Rats can track odors, other rats, and themselves: implications for the study of spatial behavior.
In order to demonstrate that rats solve dead reckoning (path integration) tasks in which they return to a starting location using self-movement (idiothetic) cues, it is necessary to remove external (allothetic) cues. Odor cues, especially those generated by a rat on a single passage, are difficult to control and they can potentially serve as a cue to guide a homeward trip. Because it is presently unknown whether rats can track the cues that they themselves leave, as opposed to the odor trails left by other rats, we investigated this question in the present study. A tracking task was used in which rats: (1) followed a scented string from a refuge to obtain a food pellet located on a large circular table; (2) followed odors left on the table; (3) followed odors left by the passage of another rat; or (4) followed odors left by themselves. Groups of rats were presented with strings scented with either the rat's own odor (Group Own), a conspecific's odor (Group Other), or another scent, vanilla (Group Vanilla). After training, a series of discrimination tests were given to determine the nature of the stimulus that controls scent tracking. The results indicated that Own, Other, and Vanilla groups were equally proficient in discriminating and following their respective odors. The rats were also able to follow odor trails on the table surface as well as a trail left by the single passage of another rat or their own passage. This is the first study to demonstrate that rats can discriminate between conspecific odors and their own odor left during a single passage. The results are discussed in relation to their implications for experimental methodology and olfactory contributions to spatial navigation in general and dead reckoning in particular.


Borononucleotides: synthesis, and formation of a new reversible boronate internucleosidic linkage.
The synthesis of a borononucleotide analogue of thymidine and its association towards the formation of new borono-linked dimers is described.


Endoscopic thyroid resection using cutaneous elevation in lieu of insufflation.
Laparoscopic surgery to resect cervical masses has gained increasing acceptance during the past decade. This report describes the authors' technique and experience using total video endoscopic surgery to resect thyroid masses. The video camera is introduced through a 12-mm trocar inserted via a 10-mm infraclavicular incision in the sternal line. This incision will be hidden by the patient's undergarments postoperatively. An incision for a 12-mm trocar is made in each axilla, with additional incisions in the anterior chest made as necessary for the endoscope and instruments. Excellent exposure is produced by elevating the skin with hooks rather than by using carbon dioxide insufflation. This method reduces the incidence of subcutaneous emphysema and pneumomediastinum. Twenty-two thyroid lesions were resected using total video endoscopic surgery (adenoma, 13; cancer, 5; benign cyst, 3; and Graves' disease, 1). Procedures included thyroidectomy (12), thyroidectomy and isthmusectomy (4), and subtotal thyroidectomy (2). Subtotal cervical adenectomy was performed in 3 patients with papillary carcinoma. Cosmetic results were excellent. Endoscopic surgery of the neck is safe, minimally invasive, and produces excellent cosmetic results. However, it is in an early stage of development. Techniques have yet to be standardized, and specialized instruments are not available. The field is likely to mature as surgeons gain more experience.


A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib.
Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields. In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates. Generally, this procedure is reasonable, green and suitable for industrial production.


Analysis of terpenes in white wines using SPE-SPME-GC/MS approach.
Terpenes contribute to some white wines aroma, especially these produced from Muscat grapes and others aromatic ones of high terpene contents (Gewürtztramminer, Traminer, Huxel, Sylvaner). Terpenes are present in wine in free and bound (in a form of glycosides) forms. Analyses of bound terpenes are usually performed using solid phase extraction after hydrolysis of glycosides. A new method for determination of terpenes from wine, focused on determination of terpenes released after acidic hydrolysis, based on solid phase extraction (SPE) followed by solid phase microextraction (SPME) was developed. Non-polar (free) and polar (bound terpenes) fractions were separated on 500 mg C18 cartridges. Bound terpenes were sampled using SPME immediately after acidic hydrolysis in non-equilibrium conditions. Application of combined SPE-SPME approach allowed quantification of selected terpenes in lower concentrations than in SPE approach and added a selectivity to the method, which enabled detection of compounds non-detectable in SPE extracts. Results obtained by SPE and SPE-SPME approach were correlated for free terpenes and those released after acid hydrolysis 20 white wines obtained from different grape varieties (R(2)=0.923). Although developed for wine terpenes analysis, SPE followed by SPME approach has a great potential in analysis of other bound wine flavor compounds, especially those potent odorants present in trace amounts.


New nematode species, Orientatractis mekongensis n. sp. (Atractidae) and Neosynodontisia suratthaniensis n. g., n. sp. (Pharyngodonidae) from freshwater fishes in Thailand.
Based on light and scanning electron microscopical studies, two new species of nematode parasites are described from freshwater fishes in Thailand: Orientatractis mekongensis n. sp. (Atractidae) from the intestine of Pangasius bocourti Sauvage (type-host) and Helicophagus leptorhynchus Ng & Kottelat (both Pangasiidae, Siluriformes), and Neosynodontisia suratthaniensis n. sp. (Pharyngodonidae) from the intestine of Labiobarbus siamensis (Sauvage) (Cyprinidae, Cypriniformes), for which a new genus Neosynodontisia n. g. is established. Orientatractis mekongensis is mainly characterised by the number and distribution of caudal papillae (2 preanal, 1 adanal and 5 postanal pairs), the length of the left spicule (306-384 µm) and large body sizes (length of males and gravid females 5.4-6.7 mm and 7.8-9.0 mm, respectively). Neosynodontisia differs from other pharyngodonid genera with representatives parasitic in fishes not only by some morphological features (mouth withdrawn into the cephalic end with inflated cuticle, structure of the male caudal end, filamented eggs), but mainly by the occurrence of males inside the body of females. A key to the genera of the Pharyngodonidae with representatives parasitising fishes is provided.


Clinical analysis of 15 patients with relapsing auricular polychondritis.
Relapsing polychondritis (RP) is a rare autoimmune disorder of unknown etiology. The disease is characterized by episodic inflammation and destruction of cartilaginous and connective tissue structures, including the ear, eye, nose, larynx, trachea, bronchi, joints, skin, heart valves, and aorta. As the symptoms of RP are diverse and complex, it is easily misdiagnosed. The aim of this paper was to improve the understanding of the clinical features of RP, thereby facilitating its early diagnosis. Fifteen patients with RP were analyzed retrospectively and the relevant literature reviewed. The number of patients presenting with auricular chondritis was 13, while two presented with polyarthritis. Among them, the treatment of 2 RP patients with respiratory tract involvement failed and 1 patient died. Eleven patients with RP (73 %) were initially misdiagnosed. RP involves cartilage and connective tissue. The prognosis for patients with respiratory tract involvement is poor. RP causes episodic and progressive inflammation of cartilage throughout the body and is associated with a variety of clinical manifestations. Early diagnosis of RP depends on a thorough understanding of its clinical features.