Opioid peptides in blood and cerebrospinal fluid during acute stress.
The opioid peptides beta-endorphin and [met]enkephalin are present in the peripheral circulation. Plasma beta-endorphin originates from the pituitary gland and its cosecretion with ACTH is stimulated by a variety of noxious stimuli. Although the adrenal medulla contains high concentrations of [met]enkephalin-containing polypeptides which are costored with catecholamines, and although the adrenal gland appears to secrete [met]enkephalin into the adrenal vein, the relative adrenal contribution to plasma [met]enkephalin appears to be negligible. Plasma concentrations of immunoreactive [met]enkephalin may be increased by insulin and by endotoxic shock, but they are not significantly altered by acute haemorrhagic stress nor by surgical stress. Thus blood plasma concentrations of beta-endorphin, but not of [met]enkephalin, are generally increased during acute stress. The physiological significance of endogenous opioids in the circulation is not known. It is unlikely that transient increases in the concentrations of opioid peptides in peripherally circulating blood modulate nociception, since the peptides do not enter ventricular cerebrospinal fluid in detectable amounts under these conditions. Recent evidence has raised the possibility that circulating opioids may be involved in regulating blood glucose and in activating the immune system. It is also possible that circulating beta-endorphin and related polypeptides have non-opioid actions on a variety of peripheral tissues.


Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol.
The glutamatergic system may be relevant to the pathophysiology of psychosis and to the effects of antipsychotic treatments. We investigated a set of 62 SNPs located in genes coding for subunits of glutamatergic receptors (GAD1, GRIA1, GRIA3, GRIA4, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIN2B, GRM1 and GRM4), and the transporter of glycine (SLC6A5), as modulators of the effects of haloperidol. We studied a sample of 101 acutely ill psychotic patients. We then validated our result in two independent samples from Slovenia (n=71 and n=118) of schizophrenic patients treated with antipsychotics. We both investigated the antipsychotic effect (Positive and Negative Syndrome Scale) and motor side effect (Extrapyramidal Symptom Rating Scale) at baseline and days 3, 7, 14, 21 and 28. SLC6A5 variant (rs2298826) was found to be associated with a rapid rise of motor side effects at the beginning of the treatment (repeated measures of analysis of variance, P=0.0002), followed by a subsequent adaptation, probably dependent on haloperidol doses down titration. A specific effect was noted for dyskinetic symptoms. Haplotype analysis strengthened the relevance of SLC6A5: the C-A-C haplotype (rs1443548, rs883377, rs1945771) was found to be associated with higher Extrapyramidal symptom rating scale scores (overall P=0.01, haplotype P=0.000001). We successfully replicated this finding in the two independent samples from Slovenia. This result further stresses the relevance of the glutamatergic system in modulating the effects of haloperidol treatment, especially with regards to motor side effects.


Ablation of Persistent Atrial Fibrillation: AF Termination is the End Point.
This article reviews the literature on various techniques in the ablation of persistent AF, with the aim of highlighting the role of intraprocedural arrhythmia termination, defined as conversion to sinus rhythm or intermediate atrial tachycardia, in the predictability of arrhythmia recurrence. Because arrhythmia termination is not observed universally as a procedural end point, only those studies wherein it has been specifically reported, and its predictive role in arrhythmia recurrence is considered, are described.


Leucas aspera (Willd.) Link Essential Oil from India: β-Caryophyllene and 1-Octen-3-ol Chemotypes.
Leucas aspera (Willd.) Link (Lamiaceae) is an annual, branched herb used in traditional medicine as an antipyretic and insecticide. The hydro-distilled essential oil was obtained from the aerial parts of L. aspera growing wild in North West Karnataka region of India and analyzed by gas chromatography equipped with flame ionization detector and gas chromatography coupled with mass spectrometry. Forty-three compounds were identified, representing 98.1% of the total oil. The main constituents were identified as β-caryophyllene (34.2%), 1-octen-3-ol (14.8%), α-humulene (6.3%), α-pinene (5.8%), epi-α-bisabolol (4.6%) and limonene (4.5%). The oil was found to be rich in sesquiterpene hydrocarbons (47.7%), followed by others (long chain hydrocarbons (LCH), oxygenated LCH and phenyl derivative constituents) (20.2%), monoterpene hydrocarbons (14.8%), oxygenated sesquiterpenes (14.8%) and oxygenated monoterpenes (0.6%) type compounds.


The selective localization of B lymphocytes in the spleen and the role of complement receptors.
The role of complement receptors on the localization of T and B cells in the spleen of mice was studied using short-term homing experiments in cobra venom factor (CoF)-treated animals. The localization ratio of B and T cells in the spleen of CoF-treated mice decreased significantly compared to control recipients. No changes could be found in the relative distribution of resident T and B cells in the spleen or other lymphoid organs of CoF-treated animals and when their spleen or lymph node cells were transferred, the localization pattern was normal. When cells were incubated in serum prior to transfer a disturbed localization ratio in the spleen of untreated recipients was observed. This was due to a blockade of complement receptors as determined by the inability of the incubated cells to form EAC rosettes. No blockade of EAC rosettes and no changes in localization ratios upon transfer could be observed when the cells were incubated in functionally C3-depleted serum. The results suggest a role for the complement-receptor on B cells in the initial localization in the spleen, whereas no influence upon the selective localization in high endothelial venules-bearing organs was found.


Functional Nucleic Acid Nanomaterials: Development, Properties, and Applications.
Functional nucleic acid (FNA) nanotechnology is an interdisciplinary field between nucleic acid biochemistry and nanotechnology that focuses on the study of interactions between FNAs and nanomaterials and explores the particular advantages and applications of FNA nanomaterials. With the goal of building the next-generation biomaterials that combine the advantages of FNAs and nanomaterials, the interactions between FNAs and nanomaterials as well as FNA self-assembly technologies have established themselves as hot research areas, where the target recognition, response, and self-assembly ability, combined with the plasmon properties, stability, stimuli-response, and delivery potential of various nanomaterials can give rise to a variety of novel fascinating applications. As research on the structural and functional group features of FNAs and nanomaterials rapidly develops, many laboratories have reported numerous methods to construct FNA nanomaterials. In this Review, we first introduce some widely used FNAs and nanomaterials along with their classification, structure, and application features. Then we discuss the most successful methods employing FNAs and nanomaterials as elements for creating advanced FNA nanomaterials. Finally, we review the extensive applications of FNA nanomaterials in bioimaging, biosensing, biomedicine, and other important fields, with their own advantages and drawbacks, and provide our perspective about the issues and developing trends in FNA nanotechnology.


Prevalence of physical violence against children in Haiti: A national population-based cross-sectional survey.
Although physical violence against children is common worldwide, there are no national estimates in Haiti. To establish baseline national estimates, a three-stage clustered sampling design was utilized to administer a population-based household survey about victimization due to physical violence to 13-24 year old Haitians (n=2,916), including those residing in camps or settlements. Descriptive statistics and weighted analysis techniques were used to estimate national lifetime prevalence and characteristics of physical violence against children. About two-thirds of respondents reported having experienced physical violence during childhood (67.0%; 95% CI 63.4-70.4), the percentage being similar in males and females. More than one-third of 13-17 year old respondents were victimized in the 12 months prior to survey administration (37.8%; 95% CI 33.6-42.1). The majority of violence was committed by parents and teachers; and the perceived intent was often punishment or discipline. While virtually all (98.8%; 95% CI 98.0-99.3) victims of childhood physical violence were punched, kicked, whipped or beaten; 11.0% (95% CI 9.2-13.2) were subject to abuse by a knife or other weapon. Injuries sustained from violence varied by victim gender and perpetrator, with twice as many females (9.6%; 95% CI 7.1-12.7) than males (4.0%; 95% CI 2.6-6.1) sustaining permanent injury or disfigurement by a family member or caregiver (p-value<.001). Our findings suggest that physical violence against children in Haiti is common, and may lead to severe injury. Characterization of the frequency and nature of this violence provides baseline estimates to inform interventions.


Post-hypoxic myoclonus induces Fos expression in the reticular thalamic nucleus and neurons in the brainstem.
Post-hypoxic myoclonus is a movement disorder characterized by brief, sudden involuntary muscle jerks. Although the mechanism underlying this disorder remains unclear, earlier pharmacological studies indicated that aberrant activity of specific neuronal circuitry in the central nervous system causes this disorder. In the present study, Fos protein, an immediate-early gene product, was used as a marker of neuronal activity to identify the brain nuclei possibly involved in post-hypoxic myoclonus. We found that Fos protein was immunologically detected in the reticular thalamic nucleus (RT), the medial longitudinal fasciculus (MLF) as well as in the locus coeruleus (LC) and the periventricular gray substance (PVG) in post-hypoxic rats that developed myoclonus in response to auditory stimuli. Fos was not detected in these nuclei from rats that underwent 4 min of cardiac arrest without myoclonus. Electrolytic lesions of the RT or MLF but not the LC/PVG significantly reduced auditory stimulated myoclonus in the post-hypoxic rats. The results suggest that neuronal activity in the RT and the MLF plays a contributing role in post-hypoxic myoclonus.


Testing psychosocial mediators of a mind-body resiliency intervention for cancer survivors.
Group-based mind-body interventions such as the Stress Management and Resiliency Training-Relaxation Response Resiliency Program (SMART-3RP) hold promise for enhancing resiliency among cancer survivors. Mechanisms underlying improvements in psychological outcomes are theoretically established but remain unexamined empirically. Adult cancer survivors (n = 105) participating in the SMART-3RP completed surveys of resiliency and five hypothesized mediators: coping (ability to relax physical tension and assertive social support-seeking), mindfulness, positive affect, and worry. Pre-post intervention changes were assessed using repeated-measures t-tests. Bivariate correlations between change scores and a more conservative within-person parallel mediation model tested covariance between resiliency and mediators. Participants experienced moderate to large improvements in all patient-reported outcomes (ds = 1.01-0.46). Increased resiliency was significantly associated with increases in mindfulness, positive affect, and assertive social support-seeking (rs = 0.36-0.50); smaller associations with increased relaxation and decreased worry were not significant. Mindfulness and positive affect explained the largest proportion of variance in resiliency increase in the full multivariate model. Cancer survivors completing the SMART-3RP had increased resiliency, which was associated with improvements in mindfulness, positive affect, and the ability to assertively seek social support. Enhancing mindfulness and positive affect were critical components for enhancing resiliency. Implications for resiliency interventions with cancer survivors are discussed.


Intracardiac thrombosis and pulmonary thromboembolism during liver transplantation: A systematic review and meta-analysis.
Intracardiac thrombosis and/or pulmonary thromboembolism (ICT/PE) is a rare but devastating complication during liver transplantation. Its pathophysiology remains poorly understood, and successful treatment remains a challenge. This systematic review summarizes the available published clinical data regarding ICT/PE during liver transplantation. Databases were searched for all publications reporting on ICT/PE during liver transplantation. Data collected included its incidence, patient characteristics, the timing of diagnosis, treatment strategies, and patient outcomes. This review included 59 full-text citations. The point prevalence of ICT/PE was 1.42%. Thrombi were most often diagnosed during the neohepatic phase, particularly at allograft reperfusion. Intravenous heparin was effective in preventing early-stage thrombus from progressing further and restoring hemodynamics in 76.32% of patients it was utilized for; however, the addition of tissue plasminogen activator or sole use of tissue plasminogen activator offered diminishing returns. Despite all resuscitation efforts, the in-hospital mortality rate of an intraoperative ICT/PE was 40.42%, with nearly half of these patients dying intraoperatively. The results of our systematic review are an initial step for providing clinicians with data that can help identify higher-risk patients. The clinical implications of our results warrant the development of identification and management strategies for the timely and effective treatment of these tragic occurrences during liver transplantation.


[Intensification of the exopolysaccharide synthesis by Acinetobacter sp. on an ethanol-glucose mixture: aspects related to biochemistry and bioenergetics].
The possibility of intensifying the synthesis of microbial exopolysaccharides (EPS) by a strain of Acinetobacter sp. grown on a mixture of two substrates nonequivalent in terms of bioenergetics (ethanol + glucose) was shown. Based on theoretical calculations of the energy requirements for biomass and EPS synthesis from the energy-deficient substrate (glucose), the supplementary concentration of the energy-excessive substrate (ethanol) was determined that prevents the loss of glucose carbon that occurs when glucose is oxidized to CO2 to obtain energy for the processes of constructive metabolism. This made it possible to increase the efficiency of conversion of the substrate carbon to EPS. The introduction of ethanol into glucose-containing medium at a molar ratio of 3.1:1 allowed the amount of the EPS synthesized to be increased 1.8- to 1.9-fold; their yield relative to biomass increased 1.4- to 1.7-fold, and the yield of EPS relative to the substrate consumed increased 1.5- to 2-fold as compared to growth of the producer on single substrates. These results form the basis for the development of new technologies for obtaining secondary metabolites of practical value with the use of mixed growth substrates.


The severity of nocturnal hypoxia but not abdominal adiposity is associated with insulin resistance in non-obese men with sleep apnea.
Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients. The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference. Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (r = -0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance. Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.


Chromoblastomycosis. Report of a case from Tripoli, Libya.
A case of chromoblastomycosis which showed typical clinical and pathological features is presented from Tripoli, Libya, for record, as no cases seem to have been reported from that region.


Environmental enrichment reduces adolescent anxiety- and depression-like behaviors of rats subjected to infant nerve injury.
Infant nerve injury causes delayed adolescent neuropathic pain, but whether it also leads to psychiatric illness is unknown. Environmental enrichment (EE) increases social communication and activity. Thus, our goal was to test anxiety- and depression-like behaviors after infant peripheral nerve injury and evaluate the effect of environmental enrichment on these models of affective disorders. Open field, elevated plus maze, sucrose preference, and pain behaviors (paw withdrawal threshold, spontaneous guarding score, and cold response to acetone) were measured in rats that received infant spared nerve injury (SNI). Enzyme-linked immune absorbent assay of cytokines was performed to evaluate the inflammatory response in the brain. Then, the ability of intracerebroventricular (ICV) injection of a microglia inhibitor, minocycline (MIN), and EE (a free-running wheel, a staircase, a plastic tunnel, a raised platform, and various colored balls) to reverse the infant SNI effects on behaviors and cytokines was examined. Infant nerve injury resulted in adolescent anxiety- and depression-like behaviors. The medial prefrontal cortex, basolateral amygdala, and ventral hippocampus were skewed to a pro-inflammatory profile. ICV injection of MIN reduced anxiety- and depression-like behaviors without affecting pain behaviors. In addition, ICV MIN skewed the brain towards an anti-inflammatory profile. Finally, environmental enrichment improved anxiety- and depression-like behaviors, as well as pain behaviors. EE increased brain IL-10 and decreased IL-1β and TNF-α. Infant nerve injury induces adolescent anxiety- and depression-like behaviors and central nervous inflammation. Environmental enrichment reduces these behaviors by normalizing the inflammation balance in the brain.


Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride.
In situ gels are systems which are applied as solutions or suspensions and are capable of undergoing rapid sol-to-gel transformation triggered by external stimulus such as temperature, pH etc. on instillation. The aim of the present study was to formulate and evaluate pH responsive in-situ gel for ophthalmic delivery. Ciprofloxacin hydrochloride is popularly used as a broad spectrum antibiotic in the treatment of corneal ulcers of ocular infections. However, rapid dilution on instillation, wash out, poor retention of drug concentration delimit the therapeutic benefits of the drug when used in form of conventional eye drops. Sodium alginate, an ophthalmic gel forming mucoadhesive polymer was chosen as polymer which undergoes instantaneous gel formation due to formation of calcium alginate by virtue of its interaction with divalent cation (Ca(+2)) present in lachrymal fluid. Hydroxy Propyl Methyl Cellulose (HPMC K4M and E5 0LV) was further incorporated as a viscosity enhancer in order to achieve the desired consistency so as to facilitate sustained drug release. The developed formulations were evaluated for clarity, pH measurement, gelling capacity, drug content, rheological study, and in vitro drug release. Thus, in situ gel based systems containing gums can be a valuable approach for ophthalmic drug delivery when compared to conventional systems.


[Vaginal delivery in case of breech presentation: Impact of a service's incentive].
The mode of delivery in podalic presentation was controvertible since the 2000s, which led to a high rate of caesarean section. In our center, the delivery mode was physician-dependent before 2012. Since 2012, the management of podalic presentations was supervised by a protocol allowing a collegiate management to promote vaginal delivery. The objective of this study was to evaluate the impact of this policy on neonatal outcomes and obstetric practices. A retrospective study was carried out with comparison of 135 patients who gave birth in 2008 with 110 patients who gave birth in 2014, before and after the implementation of the protocol in a type III university maternity hospital. Two hundred and forty-five singleton pregnancies with podalic presentation and a gestational age more than 32 weeks of gestation were included in this study. The rate of vaginal delivery trial, the evolution of clinical practices and neonatal outcomes were respectively compared. One hundred and twenty-six patients who gave birth in 2008 were compared to the 105 one of 2014. The rate of successful vaginal birth trial increased from 32.7% (n=16/49) to 63.8% (n=37/58) (P>0.05) between the two periods, this induced a decrease of 16.3% of planned caesarean sections rate [(77/126) versus (47/105) (P<0.02)] and of 6.2% of emergency caesarean sections rate [(33/126) versus (21/105) (P<0.001)]. No significant difference was observed regarding neonatal outcomes. This work shows that it is possible to limit the rate of planned and emergency caesarean sections because of an incentive policy of service without impact on neonatal morbidity and mortality.


Effects of chloramphenicol on the postreplication repair and sister recombinational DNA exchanges in ultraviolet-irradiated Micrococcus luteus.
The filling of about one third of postreplication DNA gaps in u.v.-irradiated Micrococcus luteus ATCC 4698 is blocked by chloramphenicol (CA) added just before irradiation. Addition of CA 15 min after u.v.-irradiation does not prevent the complete repair of the gaps. U.v.-sensitive M. luteus mutants (ML 6 and ML 15) are identified as defective in different steps of inducible postreplication DNA repair (PRR). PRR in unexcising M. luteus strain G7 is accompanied by the transfer of about 20% of pyrimidine dimers from parental to daughter DNA strands, which indicates the existance of recombinational pathway of PRR. Recombinational PRR in M. luteus is not inhibited by CA.


ANCA-positive glomerulonephritis and IgA nephropathy in a patient on propylthiouracil.
A 14-year-old girl developed acute renal failure after 3 years therapy with propylthiouracil (PTU) for Grave's disease. Serologic evaluation showed antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 and myeloperoxidase. Renal biopsy showed a crescentic glomerulonephritis (GN) as well as evidence of IgA nephropathy (IgAN). PTU was discontinued and the patient was treated with prednisone and cyclophosphamide. ANCA became negative and renal function improved, but did not normalize. A second biopsy showed evidence of IgA nephropathy only. Propylthiouracil use has been associated with ANCA positive pauci-immune glomerulonephritis, but not with IgA nephropathy. An overlap syndrome between IgAN and ANCA-positive GN, however, has been described. This patient may have had a preexisting IgAN, with acute pauci-immune GN secondary to PTU, or this may be the first description of an overlap syndrome of IgAN and ANCA vasculitis all caused by PTU therapy.


In vivo metabolism of N-alkylamphetamines in the rat--the effect of N-alkyl chain length on oxidation of the aromatic ring.
In vivo metabolism of N-alkylated amphetamines in the rat produced 4-hydroxy- and 4-hydroxy-3-methoxy-metabolites. The relative quantities of the phenolicmetabolites formed were dependent upon the length of the N-alkyl substituent.


Issue 1 - "Update on adverse respiratory effects of outdoor air pollution" Part 2): Outdoor air pollution and respiratory diseases: Perspectives from Angola, Brazil, Canada, Iran, Mozambique and Portugal.
To analyse the GARD perspective on the health effects of outdoor air pollution, and to synthesise the Portuguese epidemiological contribution to knowledge on its respiratory impact. Ambient air pollution has deleterious respiratory effects which are more apparent in larger, densely populated and industrialised countries, such as Canada, Iran, Brazil and Portugal, but it also affects people living in low-level exposure areas. While low- and middle-income countries (LMICs), are particularly affected, evidence based on epidemiological studies from LMICs is both limited and heterogeneous. While nationally, Portugal has a relatively low level of air pollution, many major cities face with substantial air pollution problems. Time series and cross-sectional epidemiological studies have suggested increased respiratory hospital admissions, and increased risk of respiratory diseases in people who live in urban areas and are exposed to even a relatively low level of air pollution. Adverse respiratory effects due to air pollution, even at low levels, have been confirmed by epidemiological studies. However, evidence from LMICs is heterogeneous and relatively limited. Furthermore, longitudinal cohort studies designed to study and quantify the link between exposure to air pollutants and respiratory diseases are needed. Worldwide, an integrated approach must involve multi-level stakeholders including governments (in Portugal, the Portuguese Ministry of Health, which hosts GARD-Portugal), academia, health professionals, scientific societies, patient associations and the community at large. Such an approach not only will garner a robust commitment, establish strong advocacy and clear objectives, and raise greater awareness, it will also support a strategy with adequate measures to be implemented to achieve better air quality and reduce the burden of chronic respiratory diseases (CRDs).


NO/cGMP pathway is involved in exocrine secretion from rat pancreatic acinar cells.
The enzyme responsible for the synthesis of nitric oxide (NO) from L-arginine in mammalian tissues is known as nitric oxide synthase (NOS) (EC.184.108.40.206). In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic acinar cells. Treatment of rat pancreatic acinar cells with cholecystokinin-octapeptide (CCK-OP) resulted in an increase in the arginine conversion to citrulline, the amount of NOx, the release of amylase, and the level of cGMP. Especially, CCK-OP-stimulated increase of arginine to citrulline transformation, the amount of NOx and cGMP level were completely counteracted by the inhibitor of NOS, NG-monomethyl-L-arginine (MMA), by contrast, that of amylase release was partially reduced. Furthermore, MMA-induced decrease of NOS activity and amylase release showed dose-dependent pattern. The data on the time course of CCK-OP-induced citrulline formation and cGMP rise indicate that NOS and guanylate cyclase were activated by treatment of CCK-OP. However, the mechanism of agonist-stimulated guanylate cyclase activation in acinar cells remains unknown. Therefore, activation of NOS is one of the early events in receptor-mediated cascade of reactions in pancreatic acinar cells and NO, not completely, but partially mediate pancreatic enzyme exocrine secretion.


The epidemiology of endometrial and ovarian cancer.
This review highlights similarities in the epidemiology of endometrial and ovarian cancer, including highly correlated incidence rates and similar risk factor profiles. Factors that decrease risk for both cancers include a late menarche, early age at first birth, giving birth and breastfeeding, and use of oral contraceptives. Short or irregular cycles and late menopause are associated with increased risk for both. Other risk factors that appear to operate in a similar direction include decreased risk associated with IUD use or a tubal ligation, and increased risk associated with obesity, lack of exercise, and use of talc powders in genital hygiene. Estrogen excess is proposed as the underlying mechanism for most endometrial cancers, whereas incessant ovulation has been suggested as the explanation for ovarian cancer. However, an increased number of estimated ovulatory cycles correlates directly with risk for both endometrial and ovarian cancer, suggesting that reproductive tissue turnover with an accumulation of PTEN or p53 mutations represents a possible common mechanism. An immune-based explanation involving mucin proteins represents another common mechanism that could explain additional risk factors. Maintenance of ideal weight, breastfeeding children, use of oral contraceptives, and avoidance of talc powders in genital hygiene are measures that could lower the risk for both types of cancer. Careful selection of patients for prophylactic oophorectomy for those women who are coming to hysterectomy for benign disease is an additional measure to consider for ovarian cancer.


Generation of stable recombinant retroviruses containing the beta-globin genes linked to complex regulatory elements by using transient transfection.
A transient packaging method for a retroviral vector containing beta-globin sequences, mediated by Ca3(PO4)2 precipitation, generated stable recombinant beta-globin retroviruses with intact viral genomes. We suggest the use of this method as an alternative means to overcome the production of beta-globin encoding retroviruses with aberrant viral genomes using the routine packaging procedure.


HMGB1 induces macrophage pyroptosis in chronic endometritis.
Chronic endometritis (CE) reflects the local imbalance in the endometrial immune microenvironment after inflammation. High mobility group box 1 (HMGB1) is highly involved in both immunity and inflammation. In this study, we aimed to explore the roles of HMGB1 in the endometrium of patients with CE. Endometrium and uterine fluid HMGB1 were tested in a cohort of infertile patients with or without CE. Expression levels of the pyroptosis marker, gasdermin D (GSDMD)-N-terminal (NT), in the human endometrium of patients with CE and controls were determined. Next, the role of HMGB1 as a driver of macrophage pyroptosis was investigated using human THP-1 cells in vitro and a CE mouse model in vivo. High expression levels of HMGB1 in biopsied endometrial tissue and uterine fluid were confirmed in a cohort of patients with CE. Positive correlation between the number of CD138+ cells and HMGB1 mRNA expression level were detected (rs = 0.592, P < 0.001). Meanwhile, we found that GSDMD-NT expression was significantly increased in the CE endometrium at both the transcriptional and translational levels. Moreover, co-localization of GSDMD-NT and macrophages was confirmed via the double immunostaining of GSDMD-NT and CD68. In vitro experiments revealed that macrophage pyroptosis was induced by HMGB1 in human THP-1-derived macrophages. Treatment with glycyrrhizic acid, an inhibitor of HMGB1, significantly suppressed endometrial pyroptosis and inflammation in the CE mouse model. HMGB1 effectively induced macrophage pyroptosis in the human endometrium, suggesting that its inhibition may serve as a novel treatment option for CE.


Transcription factor activation and functional stimulation of human monocytes.
Activation of expression of genes encoding transcription factors: c-fos and c-jun and formation of AP1 transcriptional complex in human monocytes was investigated. It was found that lipopolysaccharide induced strongly both c-fos and c-jun expression as well as AP1 formation. Interferon gamma activated strongly c-fos and weakly c-jun and AP1. Tumor necrosis factor induced slightly c-fos and had almost no effect on c-jun and AP1. The data suggest that differences in functional responses elicited in monocytes by all three factors may be dependent on different routes on nuclear signalling employed by the factors.


Recurrence after segmental resection for colonic Crohn's disease.
Segmental colonic resection is commonly performed in patients with colorectal Crohn's disease. The aim of this study was to evaluate the outcome after segmental colonic resection and to define risk factors for re-resection. Consecutive patients who had an initial segmental colonic resection for Crohn's colitis between 1987 and 2000 were evaluated. Patients who underwent ileocolonic resection were excluded. Patient-, disease- and treatment-related variables were assessed as possible risk factors for disease recurrence. Ninety-one patients (62 women) with a median follow-up of 8.3 years were studied. Thirty patients (33 per cent) had at least one re-resection, of whom 20 finally underwent total (procto)colectomy. Female sex and a history of perianal disease were identified as independent risk factors for re-resection: odds ratio 12.52 (95 per cent confidence interval (c.i.) 2.38 to 65.84) and 13.94 (95 per cent c.i. 3.02 to 64.27) respectively. Forty (44 per cent) of the 91 patients had a stoma at the end of the study period. Of the 30 patients who had re-resection, 24 finally had a stoma. Segmental resection for Crohn's colitis is justified. Recurrence is more frequent in women and in those with a history of perianal disease.


Ring chromosome 9. 46,XY,r(9) in a male with ambiguous external genitalia.
Cytogenetic investigation of a 4-year-old boy with ambiguous external genitalia revealed a 46,XY,r(9)(p2q3) complement. The patient displayed some phenotypic characteristics common to other reported r(9) cases, in addition to ambiguous external genitalia.


Imaging in Pediatric Demyelinating and Inflammatory Diseases of the Brain- Part 1.
Imaging plays an important role in the diagnosis, management, prognostication and follow up of pediatric demyelinating and inflammatory diseases of the brain and forms an integral part of the diagnostic criteria. Conventional and advanced MR imaging is the first and only reliable imaging modality. This article reviews the typical and atypical imaging features of common and some uncommon demyelinating and inflammatory diseases with emphasis on the criteria for categorization. Imaging protocols and the role of advanced imaging techniques are also covered appropriately.


Selective arterial embolization of the brain in an inoperable arteriovenous malformation in the thalamus. A case report.
The embolization of an inoperable arteriovenous malformation of the brain using gelatin foam strips via the Seldinger technique is described. Subsequent operative ligation of the major feeding vessels was performed, with an excellent postoperative result.


Pituitary apoplexy. Association of degenerative change in pituitary ademona with radiotherapy and detection by cerebral computed tomography.
In 14 of 300 patients with pituitary adenoma, apoplexy developed with pathologic evidence of hemorrhagic necrosis and cystic change in the tumor. In five patients, apoplexy was the initial manifestation; in eight patients, it was associated with radiotherapy. In 12 other patients with pituitary tumors, sudden clinical deterioration occurred; they had predominantly cystic tumors with minor foci of hemorrhagic necrosis. In five patients, this was associated with radiotherapy. Degenerative hemorrhagic, necrotic and cystic changes occur frequently in pituitary tumors and radiation may be potentially dangerous in these cases. To avoid precipitating episodes of sudded visual and neurologic deterioration, prior aspiration and biopsy may be performed through transphenoidal approach in those with intrasellar tumors, whereas in those with extrasellar tumors, cerebral computed tomographic scan may define pathologic features of the pituitary adenoma.


Palliative and end of life care in solid organ transplantation.
Palliative care is an interprofessional approach that focuses on quality of life of patients who are facing life-threatening illness. Palliative care is consistently associated with improvements in advance care planning, patient and caregiver satisfaction, quality of life, symptom burden, and lower healthcare utilization. Most transplant patients have advanced chronic disease, significant symptom burden, and mortality awaiting transplant. Transplantation introduces new risks including perioperative death, organ rejection, infection, renal insufficiency, and malignancy. Numerous publications over the last decade identify that palliative care is well-suited to support these patients and their caregivers, yet access to palliative care and research within this population are lacking. This review describes palliative care and summarizes existing research supporting palliative intervention in advanced organ failure and transplant populations. A proposed model to provide palliative care in parallel with disease-directed therapy in a transplant program has the potential to improve symptom burden, quality of life, and healthcare utilization. Further studies are needed to elucidate specific benefits of palliative care for this population. In addition, there is a tremendous need for education, specifically for clinicians, patients, and families, to improve understanding of palliative care and its benefits for patients with advanced disease.


The nature of facilitation and interference in the multilingual language system: insights from treatment in a case of trilingual aphasia.
The rehabilitation study described here sets out to test the premise of Abutalebi and Green's neurocognitive model--specifically, that language selection and control are components of overall cognitive control. We follow a trilingual woman (first language, L1: Amharic; second language, L2: English; third language, L3: French) with damage to the left frontal lobe and left basal ganglia who presented with cognitive control and naming deficits, through two periods of semantic treatment (French, followed by English) to alleviate naming deficits. The results showed that while the participant improved on trained items, she did not show within- or cross-language generalization. In addition, error patterns revealed a substantial increase of interference of the currently trained language into the nontrained language during each of the two treatment phases. These results are consistent with Abutalebi and Green's neurocognitive model and support the claim that language selection and control are components of overall cognitive control.


Peptide inhibition of p22phox and Rubicon interaction as a therapeutic strategy for septic shock.
Sepsis is a clinical syndrome that complicates severe infection and is characterized by the systemic inflammatory response syndrome (SIRS), is a life threatening disease characterized by inflammation of the entire body. Upon microbial infection, p22phox-gp91phox NADPH oxidase (NOX) complexes produce reactive oxygen species (ROS) that are critical for the elimination of invading microbes. However, excess production of ROS represents a key element in the cascade of deleterious processes in sepsis. We have previously reported direct crosstalk between autophagy and phagocytosis machineries by demonstrating that the Rubicon protein interacts with p22phox upon microbial infection, facilitating phagosomal trafficking of the p22phox-gp91phox NOX complex to induce a ROS burst, inflammatory cytokine production, and thereby, potent anti-microbial activities. Here, we showed N8 peptide, an N-terminal 8-amino acid peptide derived from p22phox, was sufficient for Rubicon interaction and thus, capable of robustly blocking the Rubicon-p22phox interaction and profoundly suppressing ROS and inflammatory cytokine production. Consequently, treatment with the Tat-N8 peptide or a N8 peptide-mimetic small-molecule dramatically reduced the mortality associated with Cecal-Ligation-and-Puncture-induced polymicrobial sepsis in mice. This study demonstrates a new anti-sepsis therapeutic strategy by blocking the crosstalk between autophagy and phagocytosis innate immunity machineries, representing a potential paradigm shift for urgently needed therapeutic intervention against this life-threatening SIRS.


Particulate matter (PM10) as a newly identified environmental risk factor for acute gout flares: A time-series study.
This study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10μm in diameter (PM10) on occurrence of acute gout flares in the general population and identify susceptible groups accordingly. The data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PM10 and meterological measurements were provided by the Ministry of Environment and the National Meterological Office, respectively. To estimate the risk of daily ED visits due to acute gout flare, these time-series data set were analyzed using generalized additive models with Poisson distribution, including daily average PM10 level, temperature, relative humidity, day of the week, national holiday, season, and date. The risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PM10 levels significantly increased in the cumulative lag 0-7 model (relative risk, 1.018; 95% confidence interval, 1.008-1.027, P<0.001). In particular, men aged≥40 years and those with a history of diabetes mellitus or gout were significantly at a high risk of acute gout flares by subgroup analysis. Our time-series study demonstrated a modest, but significant effect of short-term exposure to PM10 on ED visits for acute gout flares. Ambient PM10 may be a newly identified environmental risk factor for acute gout flares.


Synthesis of the C(1)-C(12) segment of peloruside A by an alpha-benzyloxymethyl ketone aldol strategy.
The C(1)-C(12) segment of 16-membered antitumor macrolide peloruside A has been prepared by a BF(3).OEt(2)-catalyzed Mukaiyama aldol reaction between a glucose-derived C(1)-C(7) aldehyde and a C(8)-C(12) alpha-benzyloxymethyl ketone. Exclusive 2,3-anti and moderate 3,5-anti/syn facial selectivity (3.5:1) was observed in the aldol reaction. The key C(1)-C(7) aldehyde contains the required stereochemistry at carbons two, three, and five, and has been efficiently prepared on multigram scales from commercial triacetyl D-glucal. [reaction: see text]


Persistence of Emotional Distress in Unaccompanied Migrant Children and Adolescents Primarily From the Northern Triangle of Central America.
In the US, unaccompanied migrant children and adolescents (hereinafter referred to as children) are predominantly from Central America's Northern Triangle. While unaccompanied migrant children are at high risk for psychiatric sequelae due to complex traumatic exposures, longitudinal investigations of psychiatric distress after resettlement are lacking. To identify factors associated with emotional distress and longitudinal changes in emotional distress among unaccompanied migrant children in the US. For this retrospective cohort study, the 15-item Refugee Health Screener (RHS-15) was administered between January 1, 2015, and December 31, 2019, to unaccompanied migrant children as part of their medical care to detect emotional distress. Follow-up RHS-15 results were included if they were completed before February 29, 2020. Median follow-up interval was 203 days (IQR, 113-375 days). The study was conducted in a federally qualified health center that provides medical, mental health, and legal services. Unaccompanied migrant children who completed the initial RHS-15 were eligible for analysis. Data were analyzed from April 18, 2022, to April 23, 2023. Traumatic events before migration, during migration, during detention, and after resettlement in the US. Emotional distress, including symptoms of posttraumatic stress disorder, anxiety, and depressive symptoms, as indicated by the RHS-15 (ie, score ≥12 on items 1-14 or ≥5 on item 15). In total, 176 unaccompanied migrant children completed an initial RHS-15. They were primarily from Central America's Northern Triangle (153 [86.9%]), were mostly male (126 [71.6%]), and had a mean (SD) age of 16.9 (2.1) years. Of the 176 unaccompanied migrant children, 101 (57.4%) had screen results above the positive cutoff. Girls were more likely to have positive screen results than boys (odds ratio, 2.48 [95% CI, 1.15-5.34]; P = .02). Follow-up scores were available for 68 unaccompanied migrant children (38.6%). On the follow-up RHS-15, most scored above the positive cutoff (44 [64.7%]). Three-quarters of unaccompanied migrant children who scored above the positive cutoff initially continued to have positive scores at follow-up (30 of 40), and half of those with negative screen scores initially had positive scores at follow-up (14 of 28). Female vs male unaccompanied migrant children (unstandardized β = 5.14 [95% CI, 0.23-10.06]; P = .04) and initial total score (unstandardized β = 0.41 [95% CI, 0.18-0.64]; P = .001) were independently associated with increased follow-up RHS-15 total score. The findings suggest that unaccompanied migrant children are at high risk for emotional distress, including symptoms of depression, anxiety, and posttraumatic stress. The persistence of emotional distress suggests that unaccompanied migrant children would benefit from ongoing psychosocial and material support after resettlement.


Identification of mutaprodenafil in a dietary supplement and its subsequent synthesis.
We isolated a new illegal sildenafil analogue named mutaprodenafil from a dietary supplement for erectile dysfunction (ED) and proposed that it is an aildenafil derivative containing an imidazole moiety. We subsequently synthesized mutaprodenafil from a thioaildenafil and authenticated its structure.


Biochemical and morphologic studies of cartilage from the adult human sacroiliac joint.
The cartilage of the adult sacroiliac joint contains type II collagen and a high concentration of glycosaminoglycan. Furthermore, large aggregating proteoglycans and link proteins were extracted from the sacral cartilage. In these respects the sacroiliac cartilage is similar to that in the peripheral joints. However, while the organization of the collagen in the sacral cartilage is typical of an articular cartilage, the organization of the ilial cartilage is very different, and throughout its depth it possesses narrow collagen fibrils arranged parallel to the articular surface.


Microtubular disarray in cortical dendrites and neurobehavioral failure. II. Computer reconstruction of perturbed microtubular arrays.
A previous report details morphological alterations in dendritic structure of cortical neurons in severe neurobehavioral retardation of unknown etiology. Using computer graphic techniques, the present study describes perturbations in the 3-dimensional character of the microtubular array, which correspond to degenerative change in dendritic geometry. In large proximal processes, two types of array have been reconstructed. Segmented microtubules may form a continuous helical swirl which underlies a bulge in the dendritic cylinder. Alternatively, small groups of microtubules, while maintaining orderly internal organization, may be disoriented with respect to the long axis of the process. In varicose regions of the dendrite the microtubular array is discontinuous. Microtubules course side by side through constructed regions, only to splay out and terminate within expanded regions. These pathological alterations in the microtubular array contrast sharply with the cortical dendritic microtubular array reconstructed from the normal adult mouse. Perturbation in those parameters which determine packing of microtubules within the dendritic process is also documented. In the pathological condition, microtubules lose the ability to exclude one another from close approach. The role of cross-linking molecules in maintaining the integrity of the microtubular array, and the role of microtubules in maintaining the geometry of the dendrite, are considered.


Biochemical and enzymatic study of rice BADH wild-type and mutants: an insight into fragrance in rice.
Betaine aldehyde dehydrogenase 2 (BADH2) is believed to be involved in the accumulation of 2-acetyl-1-pyrroline (2AP), one of the major aromatic compounds in fragrant rice. The enzyme can oxidize ω-aminoaldehydes to the corresponding ω-amino acids. This study was carried out to investigate the function of wild-type BADHs and four BADH2 mutants: BADH2_Y420, containing a Y420 insertion similar to BADH2.8 in Myanmar fragrance rice, BADH2_C294A, BADH2_E260A and BADH2_N162A, consisting of a single catalytic-residue mutation. Our results showed that the BADH2_Y420 mutant exhibited less catalytic efficiency towards γ-aminobutyraldehyde but greater efficiency towards betaine aldehyde than wild-type. We hypothesized that this point mutation may account for the accumulation of γ-aminobutyraldehyde/Δ(1)-pyrroline prior to conversion to 2AP, generating fragrance in Myanmar rice. In addition, the three catalytic-residue mutants confirmed that residues C294, E260 and N162 were involved in the catalytic activity of BADH2 similar to those of other BADHs.


Enlarging premaxillary mass: A unique manifestation of extranodal diffuse B-cell lymphoma.
Lymphomas are the most common nonepithelial malignancy in the head and neck region. Among these, non-Hodgkin Lymphoma (NHL) is the most prevalent, and diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype. NHL is known for its propensity for extranodal involvement, which can affect any anatomical location. The presence of perineural spread is frequently encountered in head and neck malignancies, including lymphomas. We report a case of a 40-year-old male with an enlarging infraorbital facial mass with associated erythema, pain, and paresthesia, which was subsequently found to be extranodal DLBCL with retrograde perineural spread along the infraorbital nerve.


Combining radiomics and deep learning features of intra-tumoral and peri-tumoral regions for the classification of breast cancer lung metastasis and primary lung cancer with low-dose CT.
To investigate the performance of deep learning and radiomics features of intra-tumoral region (ITR) and peri-tumoral region (PTR) in the diagnosing of breast cancer lung metastasis (BCLM) and primary lung cancer (PLC) with low-dose CT (LDCT). We retrospectively collected the LDCT images of 100 breast cancer patients with lung lesions, comprising 60 cases of BCLM and 40 cases of PLC. We proposed a fusion model that combined deep learning features extracted from ResNet18-based multi-input residual convolution network with traditional radiomics features. Specifically, the fusion model adopted a multi-region strategy, incorporating the aforementioned features from both the ITR and PTR. Then, we randomly divided the dataset into training and validation sets using fivefold cross-validation approach. Comprehensive comparative experiments were performed between the proposed fusion model and other eight models, including the intra-tumoral deep learning model, the intra-tumoral radiomics model, the intra-tumoral deep-learning radiomics model, the peri-tumoral deep learning model, the peri-tumoral radiomics model, the peri-tumoral deep-learning radiomics model, the multi-region radiomics model, and the multi-region deep-learning model. The fusion model developed using deep-learning radiomics feature sets extracted from the ITR and PTR had the best classification performance, with the area under the curve of 0.913 (95% CI 0.840-0.960). This was significantly higher than that of the single region's radiomics model or deep learning model. The combination of radiomics and deep learning features was effective in discriminating BCLM and PLC. Additionally, the analysis of the PTR can mine more comprehensive tumor information.


Liquid jet delivery method featuring S100A1 gene therapy in the rodent model following acute myocardial infarction.
The S100A1 gene is a promising target enhancing contractility and survival post myocardial infarction (MI). Achieving sufficient gene delivery within safety limits is a major translational problem. This proof of concept study evaluates viral mediated S100A1 overexpression featuring a novel liquid jet delivery (LJ) method. Twenty-four rats after successful MI were divided into three groups (n = 8 ea.): saline control (SA); ssAAV9.S100A1 (SS) delivery; and scAAV9.S100A1 (SC) delivery (both 1.2 × 10¹¹ viral particles). For each post MI rat, the LJ device fired three separate 100 μl injections into the myocardium. Following 10 weeks, all rats were evaluated with echocardiography, quantitative PCR (qPCR) and overall S100A1 and CD38 immune protein. At 10 weeks all groups demonstrated a functional decline from baseline, but the S100A1 therapy groups displayed preserved left ventricular function with significantly higher ejection fraction %; SS group (60 ± 3) and SC group (57 ± 4) versus saline (46 ± 3), P < 0.05. Heart qPCR testing showed robust S100A1 in the SS (10,147 ± 3993) and SC (35,155 ± 5808) copies per 100 ng DNA, while off-target liver detection was lower in both SS (40 ± 40), SC (34,841 ± 3164), respectively. Cardiac S100A1 protein expression was (4.3 ± 0.2) and (6.1 ± 0.3) fold higher than controls in the SS and SC groups, respectively, P < 0.05.


Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers.
Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker. Charts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded. MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy. This real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.


Launaea taraxacifolia leaf partitions ameliorate alloxan-induced pathophysiological complications via antioxidant mechanisms in diabetic rats.
Launaea taraxacifolia (Wild.) Amin ex. Jeffery belongs to family Asteracaea. The plant is used for treatment of diseases and eaten as vegetable in Nigeria. This study investigated the ameliorative potentials of L. taraxacifolia leaf partitions in alloxan induced diabetic complications. Male Albino rats were divided into eleven groups of five rats each. Diabetes was induced following intraperitoneal administration of 150 mg/kg alloxan monohydrate and was treated with 200 and 300 mg/kg of each partitioned fractions. Hyperglycemia was reversed in all treated rats within seven days of treatments. Rats treated with the partitions showed significant increase in hematological parameters compared with diabetic control. N-hexane fraction had the best overall effect against oxidative stress particularly on heart and pancreas reduced glutathione (GSH), superoxide dismutase (SOD) and kidney glutathione S-transferase (GST) activities. The various degrees of degeneration observed in the kidney, liver, pancreas and heart of the untreated diabetic rats were milder in rats treated with partitions. The results therefore revealed the ameliorative potentials of the partitioned fractions of L. taraxacifolia leaf extract against diabetes mellitus complications via activation of the antioxidant enzymes.


Spontaneous iliac vein rupture showed by femoral contrast bolus: A case report.
Introduction: Spontaneous iliac vein rupture (SIVR) is an uncommon disease with less than sixty cases reported before. This disease often requires surgical intervention. SIVR has never been imaged in the literature. This report shows how to image this diagnosis. Case report: A 71-year-old female was diagnosed with SIVR with the use of CT venography. Endovascular repair with 2 endografts and a sinus XL stent was performed. Postoperatively, the patient developed abdominal compartment syndrome and a large part of the intestines had to be removed because of ischemia. Discussion: This is the first report that shows SIVR before and after endovascular treatment with the use of CT venography by injecting a contrast bolus in the femoral vein. This information is of high interest for a broad range of clinicians to show or exclude a venous abdominal bleeding in an early stage.


Efficacy and safety of chronic antimicrobial suppression therapy for left ventricular assist device driveline infections: A single-center descriptive experience.
Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short-term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous-flow LVADs placed between August 2007 and July 2019. A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48-2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression.


The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors.
We have investigated the possibility of a direct regulatory effect of gonadotrophin releasing hormone (GnRH) analogues on prostatic cancer cell growth. Here we report high affinity binding (Kd = 50 nM) of a GnRH analogue resulting in biphasic growth modulation of the human androgen-sensitive prostatic cancer cell line LNCaP. In contrast, the human androgen-insensitive prostatic cancer cell line DU145 showed low-affinity (Kd = 10 microM) binding without any biological response to the GnRH analogue. A GnRH-specific radioimmunoassay demonstrated GnRH-like immunoreactivity in the concentrated culture medium from both cell lines. Seventy-six human benign and malignant tumours were assayed following surgical resection. Nineteen of 22 (86%) malignant tumours and 49 of 54 (91%) benign tumours, exhibited high affinity GnRH-analogue binding. Fourteen of 19 (74%) malignant tumours and 17 of 49 (35%) benign tumours exhibiting high affinity binding contained GnRH-like immunoreactivity, suggesting that this system may be involved in prostatic epithelial cell growth in vivo.


[Effect of insertional mutation in the cspA gene encoding the major cold-shock protein on radiation resistance of Escherichia coli].
Plasmid pCspA::Km carrying a cloned mutant allele of the cspA gene for the major Escherichia coli cold-shock protein CspA with an insertion of the kanamycin resistance gene cassette from transposon Tn903 into the core region of the coding sequence causes a 2.3-fold increase in radioresistance of wild-type E. coli cells (cspA+). The radioprotective effect of this plasmid is abolished or drastically reduced in mutants recA13 and rpoH15 defective in RecA protein and in induction of the heat-shock protein regulon, respectively. Plasmid pCspA::Km causes a 1.3-fold elevation in the resistance to gamma-irradiation of E. coli mutants with an intermediate level of radioresistance (Gamr445 and KS0160) but slightly diminishes resistance of a highly radiation-resistant Gamr445 mutant. In the chromosome of E. coli with normal DNA repair systems, the cspA::Km mutation in the homozygous state enhances resistance to the lethal effect of gamma-rays and UV light 2.9 and 1.4 times, respectively. These data suggest that the system of cold-shock proteins can modulate resistance of E. coli cells to the lethal effect of gamma-rays and UV light.


Design, synthesis and biological evaluation of novel pyrazolo-pyrimidin-amines as potent and selective BTK inhibitors.
To discover the best-in-class Bruton's Tyrosine Kinase (BTK) inhibitors, for th treatment of autoimmune disorders like cancer (B-Cell Lymphoma (BCL)) and rheumatoid arthritis (RA), in the present investigation, novel structural optimizations were carried out. Introduction of novel bicyclic amine linkers and aromatic backbone led to series of compounds 9a-h and 14a-u. Compound 14b was found to be potent, orally bioavailable, selective and irreversible BTK inhibitor. In vitro, 14b showed IC50 of 1.0 nM and 0.8 nM, in BTK and TMD8 assays, respectively. In vivo,14b displayed robust efficacy in collagen-induced arthritis (CIA) and TMD8 xenograft models, which could be correlated with its improved oral bioavailability. In the repeated dose acute toxicity study, 14b showed no adverse changes, indicating that the BTK inhibitor 14b could be viable therapeutic option for the treatment of autoimmune disorders.


The circadian clock mutant lhy cca1 elf3 paces starch mobilization to dawn despite severely disrupted circadian clock function.
Many plants, including Arabidopsis (Arabidopsis thaliana), accumulate starch in the daytime and remobilize it to support maintenance and growth at night. Starch accumulation is increased when carbon is in short supply, for example, in short photoperiods. Mobilization is paced to exhaust starch around dawn, as anticipated by the circadian clock. This diel pattern of turnover is largely robust against loss of day, dawn, dusk, or evening clock components. Here, we investigated diel starch turnover in the triple circadian clock mutant lhy cca1 elf3, which lacks the LATE ELONGATED HYPOCOTYL and the CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) dawn components and the EARLY FLOWERING3 (ELF3) evening components of the circadian clock. The diel oscillations of transcripts for the remaining clock components and related genes like REVEILLE and PHYTOCHROME-INTERACING FACTOR family members exhibited attenuated amplitudes and altered peak time, weakened dawn dominance, and decreased robustness against changes in the external light-dark cycle. The triple mutant was unable to increase starch accumulation in short photoperiods. However, it was still able to pace starch mobilization to around dawn in different photoperiods and growth irradiances and to around 24 h after the previous dawn in T17 and T28 cycles. The triple mutant was able to slow down starch mobilization after a sudden low-light day or a sudden early dusk, although in the latter case it did not fully compensate for the lengthened night. Overall, there was a slight trend to less linear mobilization of starch. Thus, starch mobilization can be paced rather robustly to dawn despite a major disruption of the transcriptional clock. It is proposed that temporal information can be delivered from clock components or a semi-autonomous oscillator.


Infanticide exhibited by female mice: genetic, developmental and hormonal influences.
Approximately 25-40% of 25-45 day old C57BL/6J females killed young (1-3 day old Rockland-Swiss (R-S) albino mouse pups) while similarly aged DBA/2J females were parental or ignored neonates. Beyond 45 days of age C57BL and DBA females seldom killed young. When ovariectomized at weaning and tested for infanticide at 65 days of age, DBA females rarely killed neonates while 40% of C57BL females exhibited the behavior. In contrast to DBA females, significantly more C57BL females killed young in response to the adult administration of testosterone propionate (TP) and estradiol benzoate (EB), but not dihydrotestosterone propionate (DHTP). It is tentatively proposed that strain differences in spontaneous and steroid aroused infanticide in female mice may be related to differences in the prenatal hormone environment.


Effects of Combined Use of Mother's Breast Milk, Heartbeat Sounds, and Non-Nutritive Sucking on Preterm Infants' Behavioral Stress During Venipuncture: A Randomized Controlled Trial.
Even routine procedures can cause pain and stress, and can be harmful to the fast-growing brain of preterm infants. Mitigating pain and stress with sucrose and analgesics has side effects; thus, an alternate choice is the use of natural breast milk and infants' sensory capabilities. Therefore, this study examined the effects of different integrations of sensory experiences-mother's breast milk odor and taste (BM-OT), heartbeat sounds (HBs), and non-nutritive sucking (NNS)-on preterm infant's behavioral stress during venipuncture. This study was a prospective, randomized controlled trial. Infants born preterm (<37 weeks' gestational age) were enrolled in the study through convenience sampling, and randomly assigned to the following conditions: (condition 1) routine care (n = 36); (condition 2) BM-OT (n = 33); (condition 3) BM-OT + HBs (n = 33); or (condition 4) BM-OT + HBs + NNS (n = 36). Crying duration from puncture to recovery period was recorded using a voice recorder. Facial actions and body movements were measured using an infant behavioral coding scheme and transformed into frequencies during seven stages: baseline (stage 0), disinfecting (stage 1), venipuncture (stage 2), and the recovery period for 10 minutes (stages 3-6). Data were analyzed for 138 preterm infants. The corresponding median times to stop crying for conditions 1, 2, 3, and 4 were 137, 79, 81, and 39 s, respectively; the instantaneous occurrence rates of stopping crying for conditions 2, 3, and 4 were 1.469, 1.574, and 2.996 times greater than for condition 1, respectively. Infants receiving conditions 3 and 4 had significantly fewer occurrences of facial actions (stage 6 and stages 4-6, respectively) and body movements (stages 3-6 for both); however, there were no significant reductions in stress behaviors for condition 2 (BM-OT). The combination of BM-OT, HBs, and NNS could be provided to preterm infants as interventions to prevent and reduce behavioral stress, and facilitate pain recovery during venipuncture procedures. Clinicians should be educated about how to recognize preterm infants' behavioral stress, and to incorporate different sensory combinations of respective mothers' BM, HBs, and NNS into painful procedures to help preterm infants recover from distress.


A comparison of intra-articular hyaluronan injection accuracy rates between three approaches based on radiographic severity of knee osteoarthritis.
To compare the accuracy rates of intra-articular hyaluronic acid (HA) injections for osteoarthritis (OA) of the knee between the modified Waddell approach (an anteromedial approach with manipulative ankle traction at 30 degrees of knee flexion), an anteromedial approach with the subjects seated (hereinafter the seated anteromedial approach) and a lateral patellar approach based on the Kellgren-Lawrence (K-L) radiographic grade (II, III and IV). Fifty patients with knee OA received HA injections through the three approaches. The accuracy rates were confirmed with a single radiograph after injections of a mixture of radiographic contrast medium. In the K-L grade IV cases (n=11), the accuracy rates through the modified Waddell approach (11 out of 11, 100%) were significantly higher than those through the seated anteromedial approach (six out of 11, 55%) and the lateral patellar approach (six out of 11, 55%) (P=0.035). No significant differences were detected in the accuracy rates of the participants classified as grade II (n=21) or III (n=18) cases between the modified Waddell approach (86% and 78%, respectively), the seated anteromedial approach (71% and 56%, respectively) and the lateral patellar approach (86% and 61%, respectively) (P>0.05). Although previous studies have been conducted on the accuracy of needle placement into the intra-articular space of the knee, no evaluations were performed with the results categorized by radiographic severity. This study highlighted the need for clinicians to change the approach employed for HA injections, according to the severity of knee OA.


Association of social capital with obesity among older adults in China: a cross-sectional analysis.
Under the global aging trend, health issues of the elderly have received more and more attention. Among them, older adults' obesity is one of the common health problems of the elderly. The association between social capital and obesity in the older adults has been analysed and discussed in previous studies but remains controversial. There are few studies on the association between social capital and obesity in the older adults in China. We examined whether social capital was associated with obesity in Chinese older adults. The data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) -wave 8 (2017-2018) was used in this study. Totally, 10,164 respondents were included in the final analysis. Generalized trust, social participation (informal social interaction and participation of organized social activities), and social support was used as measures of social capital. Obesity status was defined by body mass index (BMI). Logistic regression analyses were used to assess associations between the social capital and obesity, adjusting for confounders. We found that the older adults who did not trust people around had greater odds of being overweighted/obese compared to those who trust [Adjusted Odds Ratio (AOR) 1.155, 95% CI 1.045 to 1.265]. The older adults having formal participation (participating in organized social activities) registered considerably higher BMI (AOR 1.155, 95% CI 1.041 to 1.269). The older adults who did not trust people around them had greater odds of being overweighted/obese both in males (AOR 1.172, 95% CI 1.012-1.333) and in females (AOR 1.155, 95% CI 1.004-1.306). Males having formal social participation were more likely to be overweighted/obese (AOR 1.181, 95% CI 1.024 to 1.337), but not in females. Generalized trust and formal social participation was associated with overweight/obesity among older adults in China. Targeted obesity interventions for older adults are needed by developing public health policies for social capital optimization.


Nutrigenomics in livestock-recent advances.
The study of the effects of nutrients on genome functioning, in terms of gene transcription, protein levels, and epigenetic mechanisms, is referred to as nutrigenomics. Nutrigenomic studies in farm animals, as distinct from rodents, are limited by the high cost of keeping livestock, their long generational distance, and ethical aspects. Yet farm animals, and particularly pigs, can serve as valuable animal models for human gastrological diseases, since they possess similar size, physiology, and nutritional habits and can develop similar pathological states. In livestock, the effects of dietary modifications have mostly been studied with reference to effective breeding and their influence on production traits and animal health. The majority of such studies have looked at the impact of various sources and quantities of fat and protein, supplementation with microelements, and plant-derived additives. The period of life of the animal-whether prenatal, neonatal, or mature-is typically considered when a modified diet is used. This review presents a summary of recent nutrigenomic studies in livestock.


Human cytomegalovirus stimulates cellular IKK2 activity and requires the enzyme for productive replication.
Human cytomegalovirus (HCMV) exploits the host transcription factor NF-kappaB to enhance its own replication, dissemination, and reactivation from latency. Here we report that HCMV infection activates the upstream IkappaB kinase (IKK) complex and that its catalytic IKK2 subunit is required for HCMV-induced NF-kappaB activation, as well as the replication of different HCMV strains. These results indicate that IKK2 is essential for HCMV replication and emphasize the feasibility of blocking NF-kappaB activation as a way of inhibiting infection.


Laparoscopic repair of traumatic perforation of the urinary bladder.
Laparoscopy as a diagnostic modality in trauma has been reported. However, therapeutic laparoscopy for trauma remains a controversial subject. We present a case of laparoscopic repair of a traumatic bladder rupture. A 25-year-old man was brought to the emergency room after a head-on collision. Physical examination was unremarkable with the exception of gross hematuria upon insertion of a urinary catheter. Computed tomography scan of the abdomen demonstrated a small amount of free intraperitoneal fluid. An anteroposterior cystogram was obtained which showed no intraperitoneal or extraperitoneal leak. Repeat examinations of the abdomen revealed a mild tenderness in the lower abdomen. Because of the presence of unexplained free intraperitoneal fluid and equivocal signs of peritoneal irritation, exploratory laparoscopy was performed. Three 5-mm ports and a 5-mm laparoscope were used. Laparoscopic examination of the abdomen revealed a 4-cm rupture at the dome of the bladder. The laceration was sutured in two layers using an intracorporeal technique. The patient was discharged on the second postoperative day with indwelling urinary catheter. Eight days after the operation, a repeated cystogram revealed no evidence of leak. We believe that laparoscopic exploration for trauma in hemodynamically stable patients is feasible. The repair of simple intraabdominal injuries such as bladder rupture can be safely performed.


Analysis of differences in the accumulation of tea compounds under various processing techniques, geographical origins, and harvesting seasons.
The processing techniques, geographical origins, and harvesting seasons have a significant impact on tea compound accumulation, leading to different flavor characteristics and consumer preferences for tea. Herein, six categories of tea involving 1329 samples revealed the distribution characteristics via compound accumulation, as well as the impact of production regions and harvesting seasons on flavor chemicals. With the increasing fermentation degree, the average content of tea polyphenols, catechins, and theanine in dark tea decreased by 57.78%, 94.64%, and 98.57% compared to green tea, respectively. The compounds in tea fluctuate with the geographical origins and seasons, with theanine and free amino acids being more accumulated in the Jiangnan tea region in spring tea, while total polyphenols and catechins were more abundant in Southwest China's tea region in summer and autumn tea. This study comprehensively understands the accumulation characteristics of tea compounds corresponding to processing techniques and the geographical origins of Chinese tea.


Charge-fluctuation contribution to the Raman response in superconducting cuprates.
We calculate the Raman response contribution due to soft collective modes, finding a strong dependence on the photon polarizations and on the characteristic wave vectors of the modes. We compare our results with recent Raman spectroscopy experiments in underdoped cuprates, La2-xSrxCuO4 and (Y1.97Ca0.3)Ba2CuO6.05, where anomalous low-energy peaks are observed, which soften upon lowering the temperature. We show that the specific dependence on doping and on photon polarizations of these peaks can naturally arise from charge collective excitations at finite wavelength.


Giant duodenal ulcer: a dangerous variant of a common illness.
Giant duodenal ulcers are large posterior penetrations of the duodenum which, when undiagnosed, have a high mortality. Radiographic and endoscopic diagnosis, although not always feasible, enables prompt appropriate management with improved results. Nonoperative treatment is dangerous. Preoperative diagnosis permits planned operative treatment and enables the surgeon to avoid a difficult duodenal dissection. The Bancroft operation, or modification thereof, is the operation of choice. Sixteen consecutive patients with giant duodenal ulcer are described. The success of their treatment is attributed to accurate diagnosis and appropriate operative therapy.


5-Lipoxygenase is involved in the angiotensin II-induced NAD(P)H-oxidase activation.
Angiotensin II (ANG II)-induced interleukin (IL)-6 synthesis requires NAD(P)H-oxidase-derived superoxide anions. Since NAD(P)H-oxidase activation by cytokines involves 5-lipoxygenase (LOX)-derived leukotriene B(4) (LTB(4)) formation, we postulated that LTB(4) is involved in the ANG II-dependent NAD(P)H-oxidase activation. Therefore, 5-LOX expression and LTB(4) formation following ANG II (100nM) stimulation were determined in rat aortic smooth muscle cells (SMC). Reactive oxygen species (ROS)-formation and IL-6 mRNA expression were analyzed following ANG II and LTB(4) (0.6 microM) stimulation. 5-LOX mRNA and protein were detected in SMC. ANG II-induced LTB(4) formation at 2.5min and was followed by an increase in ROS-formation and IL-6 mRNA expression. Blockade of 5-LOX by MK886 (200nM) abrogated LTB(4)-formation, ROS-formation, and IL-6 mRNA expression. Moreover, LTB(4)-induced ROS-formation and IL-6 mRNA expression was abolished by NAD(P)H-oxidase inhibition using diphenyleneiodonium chloride (DPI 10 microM). In conclusion, the present study demonstrates that ANG II enhances LTB(4)-formation in an 5-LOX dependent manner. LTB(4) activates the vascular type NAD(P)H-oxidase, leading to an increase in IL-6 transcripts.


Strength-duration properties and excitability of motor and sensory axons across different target thresholds.
The present series of studies aimed to investigate the biophysical basis underlying differences in behavior between motor and sensory axons at different target response levels. In 24 healthy individuals, axonal excitability protocols measured strength-duration properties and latent addition across several axonal populations, with target amplitudes set at 10%, 20%, 40%, and 60%. Strength-duration time constants (SDTCs) were typically longer at lower target levels for both motor and sensory axons. Threshold change at 0.2 ms during assessment of latent addition, representing a persistent Na+ current (Nap), was higher in sensory axons. Passive membrane properties were not different across target levels. Significant relationships were evident between the threshold change at 0.2 ms and SDTC across all target levels for motor and sensory axons. These differences were explored using mathematical modeling of excitability data. With decreasing target size, as the internodal leak conductance increased in sensory axons, the Barrett-Barrett conductance decreased, whereas the hyperpolarization-activated cation current (Ih) channels became more depolarized. A similar pattern was observed in motor axons. As such, it was concluded that Nap was not responsible for the differences observed in SDTC between different target levels, although within specific target levels, Nap changes contributed to the variability of SDTC. This study provides a comprehensive assessment of Nap current, SDTC, and outlines key factors operating at different target levels in motor and sensory axons. Findings from the present study may point to the contributing factors of symptom development in human neuropathy.NEW & NOTEWORTHY This study provides a comprehensive assessment concerning the strength-duration behavior of motor and sensory axons at differing target levels of the compound nerve response. Strength-duration time constant was increased at lower target response levels particularly for sensory axons, whereas threshold change at 0.2 ms and passive membrane properties were not different. The results have established templates for axonal behavior in normal human axons, demonstrating altered adaptive responses, presumably secondary to different patterns of nerve activation.


Incisional hernia on the 5-mm trocar port site and subsequent wall endometriosis on the same site: a case report.
A 26-year-old nulliparous woman underwent a laparoscopy to remove a 10-cm endometrial cyst on the left ovary (type II Nezhat). The cyst was extracted from the 10-mm umbilical incision; the other 2 trocars were inserted through 5-mm incisions. One year later, in correspondence to the previous 5-mm incision site, a hernia occurred that contained omentum and was reduced easily with a local anesthetic. After 2 years of good health, an aching nodule occurred on the same trocar site; vaginal ultrasound examination showed another left ovarian cyst. A second laparoscopy was performed; the cyst was very adherent and was removed in fragments. The wall nodule was removed, and the histologic examination classified it as endometriosis.


Oxidative damage induced by copper in mouse primary hepatocytes by single-cell analysis.
Copper can disturb the intracellular redox balance, induce oxidative stress, and subsequently cause irreversible damage, leading to a variety of diseases. In the present study, mouse primary hepatocytes were chosen to elucidate the in vitro oxidative damage of short-term copper exposure (10-200 μM) by single-cell analysis. We evaluated the toxicity of copper by reactive oxygen species (ROS), glutathione (GSH), and oxidative DNA damage at the single-cell level. Oxidative damage induced by copper was verified by the morphological changes, persistent elevations of excessive ROS and malondialdehyde (MDA), a decrease in GSH level, and the oxidative DNA damage. Furthermore, the average ROS generation, GSH consumption, and the indicators in DNA damage did not significantly change at relatively low concentrations (10 or 50 μM), but we can find the alterations of parameters in some single cells clearly. Emphasis on the analysis of single cells is conducive to gain a better understanding on the toxicity of copper. This study will also complement studies on the environmental risk assessment of copper pollution.


Camrelizumab Combined With Gemcitabine and Albumin-Bound Paclitaxel for Neoadjuvant Therapy in the Treatment of Progressive Gallbladder Cancer: A Case Report.
The roles of immune checkpoint inhibitors in the treatment of gallbladder cancer are still unclear and challenged by controversial findings. Recent research has shown that immune checkpoint inhibitors in combination with chemotherapy may alleviate disease progression. A 45-year-old female patient with gallbladder cancer accompanied by multiple abdominal lymph node metastasis was treated with camrelizumab combined with paclitaxel for injection (albumin-bound) and gemcitabine (AG) to downstage the tumor before a radical surgery could be performed. The postoperative quality of life was superior to the preoperative level. Camrelizumab + AG offers a new therapeutic option for gallbladder cancer with multiple abdominal lymph node metastasis, which, however, warrants further validation in clinical trials.


Methylation status of alu repetitive elements in children with tuberculosis disease.
Investigation of DNA methylation in Alu repetitive elements (REs) was shown to be a promising field to explore transcriptional changes in human genome under disease condition. To scrutinize the association between Alu methylation and tuberculosis (TB) disease in children, the difference in Alu DNA methylation level was compared with healthy controls. Whole-blood genomic DNA from 36 TB-infected children and 32 healthy controls was isolated, and the level of Alu repeat DNA methylation was examined by methylation-specific polymerase chain reaction. The median Alu methylation level in TB patients was 30% (Interquartile range [IQR], 25-30%), whereas in healthy controls, it was 75% (IQR, 50-75%) (P < 0.0001). The median level of DNA methylation of Alu RE in TB cases was significantly lower than healthy controls. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.969 (95% confidence interval, 0.936-1) (P < 0.0001), with 100% sensitivity and 84% specificity. Our results point out that detection of Alu DNA methylation in whole-blood DNA may be clinically useful tool for the diagnosis and prognosis of TB disease in children.


Pancreaticoduodenectomy in a government medical college-should we proceed!!!
The value of standard Pancreaticoduodenectomy for Periampullary carcinomas has long been a matter of debate. Though the mortality has dramatically reduced in high volume centers with dedicated hepatobiliary surgery units, the rate is still high in peripheral institutes. In this study our aim was to access the overall post operative outcome associated with pancreaticoduodenectomy performed in a government medical college. A total of 44 patients who underwent pancreaticoduodenectomy for operable periampullary cancers were evaluated. The overall morbidity rate was 31.1%. A total of 13 (29.5%) died following the operation and of its complications though the rate has reduced drastically to 14.2% in2008. The average length of hospital stay was 22 days. The mean survival was 15 months. Pancreaticoduodenectomy can safely be performed in government medical colleges with good results. In view of the majority of the patients in rural and suburban communities, not all patients need referral to higher centers.


Comparison of morphological and molecular genetic quantification of relative abundance of arbuscular mycorrhizal fungi within roots.
Nested PCR amplicons of ribosomal RNA genes have been used to identify individuals within assemblages of arbuscular mycorrhizal (AM) fungi in roots and to estimate their relative abundance. Microscopy has also been used to identify their relative abundance in roots, but only at low resolution, usually the genus level. We evaluated the robustness of using nested PCR amplicons of ribosomal RNA genes to estimate the relative abundance of undefined AM fungi in uniformly aged roots in comparison to visual estimates. The relative abundance of AM fungi was assessed as per cent root length colonised by morphotypes and relative sequence type abundance in clone libraries. Plants were grown in coastal soil to obtain assemblages of unknown AM fungi at two times (spring and autumn). Relative abundance of dominant genera of AM fungi in roots (Archaeospora and Glomus) based on an analysis of ribosomal RNA genes did not consistently correspond with relative abundance of morphotypes. This microscopic vs. molecular genetic comparison supports previous conclusions that there can be limitations in using nested PCR amplicons for quantifying the relative abundance of AM fungi in roots, with a sampling bias likely to be of significance. Both molecular genetic and morphological methods are used to estimate relative abundance of AM fungi as a precursor to understanding mycorrhizal function in field soils, but they are rarely verified using alternative approaches although this may be necessary.


Validity of utility measures for women with pelvic organ prolapse.
Pelvic organ prolapse is a common condition that frequently coexists with urinary and fecal incontinence. The impact of prolapse on quality of life is typically measured through condition-specific quality-of-life instruments. Utility preference scores are a standardized generic health-related quality-of-life measure that summarizes morbidity on a scale from 0 (death) to 1 (optimum health). Utility preference scores quantify disease severity and burden and are widely used in cost-effectiveness research. The validity of utility preference instruments in women with pelvic organ prolapse has not been established. The objective of this study was to evaluate the construct validity of generic quality-of-life instruments for measuring utility scores in women with pelvic organ prolapse. Our hypothesis was that women with multiple pelvic floor disorders would have worse (lower) utility scores than women with pelvic organ prolapse only and that women with all 3 pelvic floor disorders would have the worst (lowest) utility scores. This was a prospective observational study of 286 women with pelvic floor disorders from a referral female pelvic medicine and reconstructive surgery practice. All women completed the following general health-related quality-of-life questionnaires: Health Utilities Index Mark 3, EuroQol, and Short Form 6D, as well as a visual analog scale. Pelvic floor symptom severity and condition-specific quality of life were measured using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire, respectively. We measured the relationship between utility scores and condition-specific quality-of-life scores and compared utility scores among 4 groups of women: (1) pelvic organ prolapse only, (2) pelvic organ prolapse and stress urinary incontinence, (3) pelvic organ prolapse and urgency urinary incontinence, and (4) pelvic organ prolapse, urinary incontinence, and fecal incontinence. Of 286 women enrolled, 191 (67%) had pelvic organ prolapse; mean age was 59 years and 73% were Caucasian. Among women with prolapse, 30 (16%) also had stress urinary incontinence, 39 (20%) had urgency urinary incontinence, and 42 (22%) had fecal incontinence. For the Health Utilities Index Mark 3, EuroQol, and Short Form 6D, the pattern in utility scores was noted to be lowest (worst) in the prolapse + urinary incontinence + fecal incontinence group (0.73-0.76), followed by the prolapse + urgency urinary incontinence group (0.77-0.85) and utility scores were the highest (best) for the prolapse only group (0.80-0.86). Utility scores from all generic instruments except the visual analog scale were significantly correlated with the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire total scores (r values -0.26 to -0.57), and prolapse, bladder, and bowel subscales (r values -0.16 to -0.50). Utility scores from all instruments except the visual analog scale were highly correlated with each other (r = 0.53-0.69, P < .0001). The Health Utilities Index Mark 3, EuroQol, and Short Form 6D, but not the visual analog scale, provide valid measurements for utility scores in women with pelvic organ prolapse and associated pelvic floor disorders and could potentially be used for cost-effectiveness research.


Identification of critical active-site residues in the multifunctional human DNA repair enzyme HAP1.
All organisms express dedicated repair enzymes for counteracting the cytotoxic and mutagenic potential of apurinic/apyrimidinic (AP) lesions, which would otherwise pose a serious threat to genome integrity. We present the predicted three-dimensional structure of the major human AP site-specific DNA repair endonuclease, HAP1, and show that an aspartate/histidine pair, in conjunction with a metal ion-coordinating glutamate residue, are critical for catalyzing the multiple repair activities of HAP1. We suggest that this catalytic mechanism is conserved in certain reverse transcriptases, but is distinct from the two metal ion-mediated mechanism defined for other hydrolytic nucleases.


F-box and leucine-rich repeat protein 16 controls tamoxifen sensitivity via regulation of mitochondrial respiration in estrogen receptor-positive breast cancer cells.
Tamoxifen is one of the most effective therapeutic tools for estrogen receptor-positive (ER +) breast cancer. However, the intrinsic insensitivity and resistance to tamoxifen remains a significant hurdle for achieving optimal responses and curative therapy. In this study, we report that F-box and leucine-rich repeat protein 16 (FBXL16) is located in the mitochondria of ER + breast cancer cells. The mitochondrial FBXL16 plays an essential role in sustaining mitochondrial respiration and thereby regulates the sensitivity of ER + breast cancer cells to tamoxifen treatment. Importantly, high FBXL16 expression is significantly correlated with poor overall survival of ER + breast cancer patients. Moreover, mitochondrial inhibition phenocopies FBXL16 depletion in terms of sensitizing the ER + breast cancer cells to tamoxifen treatment. Together, our study demonstrates that FBXL16 acts as a novel regulator of tamoxifen sensitivity. Thus, targeting FBXL16 may serve as a promising approach for improving the therapeutic efficacy of tamoxifen in ER + breast cancer cells.


Management of Enteritis Associated With Tricohepatoenteric Syndrome due to SKIV2L Mutation Using the Combination of JAK1/2 Inhibition and Azathioprine.
Tricohepatoenteric syndrome is a rare genetic disorder caused by mutations in SKIV2L or TTC37. An upregulation of type 1 interferon signaling is associated with the SKIV2L variation. Introduction of Baricitinib as a JAK1/ 2 kinase inhibitor alongside traditional immunosuppressive agents successfully reduced the symptoms of enteritis by blocking the inflammogenic effects of type 1 interferonopathy in a case of tricohepatoenteric syndrome diagnosed in a 5-year-old boy.


Alcohol impairs hippocampal function: From NMDA receptor synaptic transmission to mitochondrial function.
Many studies have reported that alcohol produces harmful effects on several brain structures, including the hippocampus, in both rodents and humans. The hippocampus is one of the most studied areas of the brain due to its function in learning and memory, and a lot of evidence suggests that hippocampal failure is responsible for the cognitive loss present in individuals with recurrent alcohol consumption. Mitochondria are organelles that generate the energy needed for the brain to maintain neuronal communication, and their functional failure is considered a mediator of the synaptic dysfunction induced by alcohol. In this review, we discuss the mechanisms of how alcohol exposure affects neuronal communication through the impairment of glutamate receptor (NMDAR) activity, neuroinflammatory events and oxidative damage observed after alcohol exposure, all processes under the umbrella of mitochondrial function. Finally, we discuss the direct role of mitochondrial dysfunction mediating cognitive and memory decline produced by alcohol exposure and their consequences associated with neurodegeneration.


Mechano-stimulated modifications in the chloroplast antioxidant system and proteome changes are associated with cold response in wheat.
Mechanical wounding can cause morphological and developmental changes in plants, which may affect the responses to abiotic stresses. However, the mechano-stimulation triggered regulation network remains elusive. Here, the mechano-stimulation was applied at two different times during the growth period of wheat before exposing the plants to cold stress (5.6 °C lower temperature than the ambient temperature, viz., 5.0 °C) at the jointing stage. Results showed that mechano-stimulation at the Zadoks growth stage 26 activated the antioxidant system, and substantially, maintained the homeostasis of reactive oxygen species. In turn, the stimulation improved the electron transport and photosynthetic rate of wheat plants exposed to cold stress at the jointing stage. Proteomic and transcriptional analyses revealed that the oxidative stress defense, ATP synthesis, and photosynthesis-related proteins and genes were similarly modulated by mechano-stimulation and the cold stress. It was concluded that mechano-stimulated modifications of the chloroplast antioxidant system and proteome changes are related to cold tolerance in wheat. The findings might provide deeper insights into roles of reactive oxygen species in mechano-stimulated cold tolerance of photosynthetic apparatus, and be helpful to explore novel approaches to mitigate the impacts of low temperature occurring at critical developmental stages.