A new in vitro bioassay for human calcitonin: validation and comparison to the rat hypocalcemia bioassay.
The human breast cancer cell line T 47 D expresses calcitonin (CT) receptors that are coupled to adenylate cyclase and which reveal a dose-dependent cyclic AMP response to CT. We used this model to establish an in vitro bioassay for synthetic human CT (hCT) preparations to overcome some of the obstacles of the standard rat hypocalcemia in vivo bioassay. The detection limit of the in vitro bioassay was 1 x 10(-10) M hCT (EC 50: 8.7 pM +/- 26%) compared to 7.3 x 10(-9) M (EC 50: 7.2 microM +/- 32%) for the in vivo bioassay. The relative potencies of test preparations revealed a good correlation (r = 0.89) and several hCT-related substances produced comparable results when tested by the two methods. The standard deviations of precision and accuracy, however, were significantly smaller (P less than 0.05) for the in vitro bioassay. According to these data the T 47 D in vitro bioassay is more sensitive, superior in precision and accuracy, and comparable in specificity to the rat hypocalcemia bioassay.


A modified tracheal transection approach for cervical esophageal lesion treatment: A report of 13 cases.
Surgical interventions for tumors in the cervical esophageal region are complicated and laryngeal function is frequently sacrificed. Therefore, we attempted the tracheal transection approach to resect the tumor while preserving laryngeal function. Three patients with papillary thyroid cancer (PTC), six with cervical esophageal cancer (CEC), and four with CEC mixed with thoracic esophageal cancer (TEC) were enrolled. The esophagus was exposed after the trachea was transected between the second and third tracheal rings. CEC/TEC: Resection of the esophagus or/and a portion of the hypopharynx with acceptable safety margins and repair with free jejunum or tubular stomach. PTC: Suture the small esophageal incision immediately after removing the tumor. The tracheal dissection was repaired with interrupted sutures throughout the entire layer after the esophageal lesion was resected. The status of the recurrent laryngeal nerve (RLN) determined whether a tracheotomy was necessary. All 13 patients had effective esophageal lesion excision, with six of them requiring intraoperative tracheotomy. Postoperative complications included a tracheoesophageal fistula (one case, 7.7%), postoperative RLN paralysis (two cases, 15.4%), and aspiration (three cases, 23.1%). Except for two patients with distant metastases, there was no recurrence in the remaining patients after 5-92 months of follow-up. The tracheal transection approach, as a new surgical technique, can retain laryngeal function while ensuring appropriate exposure and satisfactory surgical resection. Before surgery, the feasibility of this approach must be carefully assessed. The RLN should be protected during the procedure. The operation is both safe and effective, with a wide range of applications.


Transcriptome of airway neutrophils reveals an interferon response in life-threatening respiratory syncytial virus infection.
Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology. We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis. Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G). Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.


Use of the indirect platelet radioactive antiglobulin test with anti-IgG and anti-C3 in immune and nonimmune thrombocytopenias.
Indirect platelet radioactive antiglobulin tests using anti-IgG and anti-C3 were performed in 483 individuals. The subjects' diagnoses and clinical states were correlated with sensitizing protein (IgG and/or C3). Sensitivity of the technique was increased by increasing the serum to cell ratio and there was good correlation between direct and indirect antiglobulin tests in 56 patients. Seven percent of normal healthy non-thrombocytopenic untransfused males and 88% of patients in whom autoimmune thrombocytopenia was clinically suspected showed a positive test result. In the indirect antiglobulin test, mean +/- SD fg anti-C3d/platelet was 1.75 +/- 0.28 (N = 58) with serum from normal subjects, 3.91 +/- 1.86 (N = 123) with serum from patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus, and 2.78 +/- 0.91 (N = 52) with serum from patients with lymphoproliferative disease. The differences were significant with P less than 0.001. Levels of bound anti-IgG were in general accord with those of other reports; there was no significant relationship with serum immunoglobulin levels. When the indirect antiglobulin tests were positive for both IgG and C3, there was a significant correlation between IgG and C3 bound to normal platelets (r = 0.671; P less than 0.01). Although sera from 39% of patients whose thrombocytopenia was not initially suspected to be on an autoimmune basis gave a positive test result, indirect platelet radioactive antiglobulin tests using anti-IgG and anti-C3 may be convenient tools in the evaluation and follow-up of immune thrombocytopenias.


Selection and validation of reference genes for normalization of quantitative real-time reverse transcription PCR analysis in Poria cocos (Schw.) Wolf (Fuling).
Quantitative real-time reverse transcription PCR (qRT-PCR) requires a stable internal control to avoid misinterpretation of data or errors for gene expression normalization. However, there are still no validated reference genes for stable internal control in Poria cocos (Schw.) Wolf (Fuling). This study aims to validate the reference genes of P. cocos. This study firstly collected the 14 candidate reference genes by BLASTP from the genome of P. cocos for qRT-PCR analysis to determine the expression levels of 14 housekeeping genes (GAPDH, MAPK, β-Act, RPB2, RPB1-1, RPB1-2, his3-1, his3-2, APT, SAMDC, RP, β-Tub, EIF, and CYP) under different temperatures and in response to different plant hormones (indole-3-acetic acid, abscisic acid, 6-benzylaminopurine, methyl jasmonate, and gibberellic acid), and the threshold cycle (Ct) values. The results were analyzed by four programs (i.e., geNorm, NormFinder, BestKeeper, and RefFinder) for evaluating the candidate reference genes. SAMDC, his3-2, RP, RPB2, and his3-1 were recommended as reference genes for treating P. cocos with indole-3-acetic acid, abscisic acid, 6-benzylaminopurine, methyl jasmonate, and gibberellic acid, respectively. Under different temperatures RPB2 was the most stable reference gene. CYP was the most stable gene for all 90 samples by RefFinder. SAMDC, his3-2, RP, RPB2, and his3-1 were evaluated to be suitable reference genes for P. cocos following different treatments. RPB2 was the most stable reference gene under different temperatures and CYP was the most stable gene in the mycelia under all six evaluated conditions.


Correlation of sequential changes in serum thyroglobulin, triiodothyronine, and thyroxine in patients with Graves' disease and subacute thyroiditis.
Serum thyroglobulin (Tg), triiodothyronine (T3), and thyroxine (T4) concentrations were measured in sera from selected patients with hyperthyroidism due to Graves' disease and with subacute thyroiditis. In agreement with previous reports, the concentration of serum Tg was elevated in untreated hyperthyroidism due to Graves' disease, being 132 +/- 124 ng/ml (mean +/- SD) as opposed to 11 +/- 6.4 ng/ml in normal subjects. During treatment of hyperthyroidism with antithyroid drugs with or without iodide, reductions in thyroid hormone concentrations were not associated with a change in serum Tg. On the other hand, marked elevations in serum Tg to concentrations as high as 7000 ng/ml were observed within 24-48 hr after subtotal thyroidectomy or 131I treatment of patients with Graves' disease. These abrupt 10-50-fold increases in serum Tg were not associated with changes in serum T3 and T4. As previously demonstrated, patients with subacute thyroiditis may have elevated serum Tg concentrations that are not associated with elevations in serum T3 and T4. Serum Tg may remain elevated long after clinical and other biochemical mainfestations of this disease have disappeared. These data suggest that the disruption in thyroid function in patients with subacute thyroiditis may persist in a subclinical form for longer periods than previously suspected. Serum Tg appears to be a sensitive indicator of acute thyroidal damage due to surgical, radiation, or inflammatory trauma. The absence of parallel changes in serum Tg, T3, and T4 indicates that release of these thyroidal components can occur by different mechanisms and that nonthyroid tissues cannot efficiently generate T3 and T4 from circulating Tg. Accordingly, local or systemic stimulation of thyroidal Tg hydrolysis may be involved in the generation of hyperthyroidism sometimes seen in patients with subacute thyroiditis.


Positive or negative ethnic encounters in urban neighbourhoods? A photo experiment on the net impact of ethnicity and neighbourhood context on attitudes towards minority and majority residents.
Using data from a new factorial survey experiment, we study the mechanisms that drive negative interethnic attitudes in urban neighbourhood encounters. Specifically, we examine the extent to which the general impression made by a resident depends on the ethnicity of that resident and on the aspects of the neighbourhood environment. Majority and minority respondents in the Netherlands judged pictures and descriptions of fictitious neighbourhood residents, in which the ethnicity of the resident varied independently of other resident characteristics (i.e., work status, religion and problem behaviour) and the neighbourhood environment (i.e., physical disorder and ethnic and socioeconomic composition). We show that outcomes depend largely on the ethnicity of the respondent who experiences the encounters. For majority respondents, we find a main net effect of resident ethnicity: native Dutch are less positive about Surinamese residents. Furthermore, we find some support for the normative fit hypothesis that states that minority respondents are less positively evaluated in stereotype-consistent neighbourhood environments: native Dutch are less positive about Moroccan residents encountered in low-status neighbourhoods.


A spectrophotometric method for the determination of 5-phosphoribosyl-1-pyrophosphate.
A new, sensitive, specific and simple spectrophotometric method for the determination of 5-phosphoribosyl-l-pyrophosphate (PRPP) is presented. PRPP is reacted with excess hypoxanthine in the presence of hypoxanthine-guanine phosphoribosyltransferase. At the end of the reaction, PRPP concentration is measured from the extent of conversion of hypoxanthine to inositate. The concentration of the purine base is determined spectrophotometrically in the presence of xanthine oxidase.


Primary and secondary intra-abdominal hypertension--different impact on ICU outcome.
To investigate the differences in incidence, time course and outcome of primary versus secondary intra-abdominal hypertension (IAH), and to evaluate IAH as an independent risk factor of mortality in a presumable risk population of critically ill patients. Prospective observational study. General intensive care unit of a university hospital. A total of 257 mechanically ventilated patients at presumable risk for the development of IAH were studied during their ICU stay and followed up for 90-day survival. Repeated measurements of intra-abdominal pressure (IAP). IAP was measured intermittently, via bladder. IAH (sustained or repeated IAP > or = 12 mmHg) developed in 95 patients (37.0%). Primary IAH was observed in 60 and secondary IAH in 35 patients. Patients with secondary IAH demonstrated a significant increase of mean IAP during the first three days (mean DeltaIAP was 2.2 +/- 4.7 mmHg), whilst IAP decreased (mean DeltaIAP -1.1 +/- 3.7 mmHg) in the patients with primary IAH. The patients with IAH had a significantly higher ICU- (37.9 vs. 19.1%; P = 0.001), 28-day (48.4 vs. 27.8%, P = 0.001), and 90-day mortality (53.7 vs. 35.8%, P = 0.004) compared to the patients without the syndrome. Patients with secondary IAH had a significantly higher ICU mortality than patients with primary IAH (P = 0.032). Development of IAH was identified as an independent risk factor for death (OR 2.52; 95% CI 1.23-5.14). Secondary IAH is less frequent, has a different time course and worse outcome than primary IAH. Development of IAH during ICU period is an independent risk factor for death.


Neuroprotective effect of neural stem cell-conditioned media in in vitro model of Huntington's disease.
Although neural stem cell (NSC) transplantation has been investigated as a promising tool for reconstituting damaged brains, recent evidences suggest that NSCs may rescue the brain via paracrine effects rather than by direct cell replacements. In this study, we attempted to determine the neuroprotective effect of NSC-conditioned media (NSC-CM) in in vitro model of Huntington's disease. Cerebral hybrid neurons (A1) were transfected with either wild-type huntingtin (18 CAG repeats) or mutant huntingtin (100 CAG repeats). At 24h after the transfection, immunocytochemical patterns of the huntingtin aggregations, as well as the level of N-terminal proteolytic cleavages of huntingtin were analyzed. Neuronal apoptosis was evaluated with flowcytometry after Annexin-V and propidium iodide (PI) staining. Cerebral hybrid neurons transfected with mutant huntingtin showed five aggregates patterns, including diffuse cytoplasmic, dispered vacuoles, perinuclear vacuoles, nuclear inclusions (NI), and cytoplasmic inclusions (CI). NSC-CM reduced the levels of nuclear and cytoplasmic inclusions. The transfection with mutant huntingtin increased the level of N-terminal cleavages, which was reduced by the NSC-CM treatment. In addition, NSC-CM reduced the Annexin-V(+)PI(+) and Annexin-V(+)PI(-) neurons which were induced by the mutant huntingtin transfection. In summary, NSC-CM was neuroprotective in in vitro model of Huntington's disease with modulating mutant huntingtin-induced cytotoxicity.


The transtibial route for femoral to anterior tibial artery bypass.
To assess the applicability of the transtibial route, via a drilled hole in the tibia, for femoral to anterior tibial artery bypass surgery. in a pilot study of 10 patients the preoperative arm/ankle systolic blood pressure indices were compared with those after operation. Patients were followed for 2 years. of the 10 patients, one was lost to follow-up and two had occlusions of their bypasses. After two years the remaining seven still had patient bypasses, with arm/ankle systolic blood pressure indices that were significantly higher than those before operation (p < 0.05). The transtibial route, via a drilled hole in the tibia, is a viable alternative to other methods for femoral to anterior tibial artery bypass surgery.


Relation between local result and total dose of radiotherapy for brain metastases.
Some studies published recently focused on the improvement of the treatment results of patients with brain metastases who underwent radiation therapy. They evaluated survival as a measure for the expected improvement, but failed to demonstrate a significant benefit from an increased total dose of radiotherapy. This study was targeted to investigate the effect of dose escalation with a different endpoint, the local response. As a first step, a retrospective analysis of 164 patients treated with a standard regimen of 10 x 3 Gy was performed to find factors correlating with the local result. All patients were systematically followed and underwent regular computed tomography (CT) examinations of the brain after irradiation. The second step was to compare, with respect to local control and survival, 39 patients treated with a total dose of 40-60 Gy with 39 patients treated with the standard regimen selected by means of a matched cohort pairs method. The retrospective analysis showed a dependence of the local result after irradiation on three parameters: diameter of brain metastases, primary tumor, and tumor histology. Small-cell and adenocarcinoma were found to be more radiosensitive than squamous-cell carcinoma. The highest radiosensitivity was found in breast cancer metastases. The matching procedure was performed with respect to those parameters and also the number of brain metastases and total cerebral tumor volume. The resulting groups were absolutely equivalent and differed only with regard to the total dose applied. The local response (complete or partial remission) was 48-52% after 30 Gy vs. 77% after 40-60 Gy (p < or = 0.05). Survival was not significantly different. A further analysis of the dose-response relationships showed the tendency of control probability to increase with total dose. This study suggests that there is a rationale for dose escalation in the treatment of brain metastases with radiotherapy, when local control is the aim. However, it seems questionable whether an improvement in survival results.


An unusual organoid nevus.
The sites of predilection, stages of development, and suggested therapy for organoid nevi are discussed herein, and the case of an unusual nevus is presented.


Role of viral vectors and virion shells in cellular gene expression.
The role of the virion shell in viral pathogenesis is relatively unknown yet the use of viral vectors in human gene transfer experiments requires an understanding of these interactions. In this study, we used DNA microarrays to identify genes modulated during pathogenic adenovirus or nonpathogenic adeno-associated virus infections. Responses to wt viruses, recombinant vectors, or empty virion particles were compared. Adeno-associated virus shells induced nearly the full complement of changes elicited by the intact virus. The cellular genes elicited a nonpathogenic response, with antiproliferative genes being induced as a cluster. In contrast, adenovirus and adenovirus empty capsid infection yielded a broader response and subset, respectively, including induction of immune and stress-response genes associated with pathogenic effects. Our studies show that the impact of the viral capsid on cellular gene expression, and potential host toxicity, must be considered independent of the vector genome for safe gene transfer in the clinic.


[Transpedicular fixation in treatment of segmental thoraco-lumbar spinal fractures].
The technique of transpedicular fixation employed in 18 patients has been presented. Satisfactory reduction with instrumentation limited to 2 segments only has been achieved. Transpedicular instrumentation allowed for early ambulation without any external immobilization.


Mortality in Russia Since the Fall of the Soviet Union.
Adult mortality increased enormously in Russia and other countries of the former Soviet Union when the Soviet system collapsed 30 years ago. What has happened to mortality in Russia since the fall of the Soviet Union? What explains the wide swings of mortality over time? This paper documents changes in mortality in Russia since 1989, and reviews the research in the economics and public health literature on the causes of the changes. The focus is on the post-2000 period, and the possible role played in recent declining mortality rates by Russia's alcohol and tobacco control policies. The two themes that emerge are (1) that government policies are critical for understanding both rising and falling male mortality over this period, and (2) that the underlying causes of the mortality crisis and its reversal are difficult to clearly identify empirically and remain, at best, partially understood, leaving much scope for future research on this issue. The online version contains supplementary material available at 10.1057/s41294-021-00169-w.


Postoperative seizure outcome and timing interval to start antiepileptic drug withdrawal: A retrospective observational study of non-neoplastic drug resistant epilepsy.
This study aimed to investigate the impact of timing interval to start AED withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1 year, 1-<2 years, and ≥2 years). The seizure outcome at the different time points after starting AED withdrawal were compared among three groups. Other factors that related to seizure recurrence and TIW were included into the multiple analysis to investigate the predictors of seizure-free. Altogether, 205 patients were involved in the study. 102 individuals (50%) had seizure recurrence and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted AED reduction and had not seizure recurrence before AED reduction. The rate of seizure-free had no significant difference among people with different TIW. Multiple analysis indicated that temporal surgery is a favorable predictor of seizure-free at the first year after starting AED withdrawal, and preoperative secondary generalized seizures is an unfavorable predictor of seizure-free at the final follow up. In patients with non-neoplastic DRE, TIW is not the mainly influence factor on seizure outcome, however, preoperative secondary generalized seizures and extra-temporal surgery are negatively associated with seizure-free.


Prolonged ethanol exposure alters glutamate uptake leading to astrogliosis and neuroinflammation in adult zebrafish brain.
High ethanol (EtOH) consumption is a serious condition that induces tremors, alcoholic psychosis, and delirium, being considered a public health problem worldwide. Prolonged EtOH exposure promotes neurodegeneration, affecting several neurotransmitter systems and transduction signaling pathways. Glutamate is the major excitatory amino acid in the central nervous system (CNS) and the extracellular glutamatergic tonus is controlled by glutamate transporters mostly located in astrocytes. Here, we explore the effects of prolonged EtOH exposure on the glutamatergic uptake system and its relationship with astroglial markers (GFAP and S100B), neuroinflammation (IL-1β and TNF-α), and brain derived neurotrophic factor (BDNF) levels in the CNS of adult zebrafish. Animals were exposed to 0.5% EtOH for 7, 14, and 28 days continuously. Glutamate uptake was significantly decreased after 7 and 14 days of EtOH exposure, returning to baseline levels after 28 days of exposure. No alterations were observed in crucial enzymatic activities linked to glutamate uptake, like Na,K-ATPase or glutamine synthetase. Prolonged EtOH exposure increased GFAP, S100B, and TNF-α levels after 14 days. Additionally, increased BDNF mRNA levels were observed after 14 and 28 days of EtOH exposure, while BDNF protein levels increased only after 28 days. Collectively, our data show markedly brain astroglial, neuroinflammatory and neurotrofic responses after an initial impairment of glutamate uptake following prolonged EtOH exposure. This neuroplasticity event could play a key role in the modulatory effect of EtOH on glutamate uptake after 28 days of continuous exposure.


Senescence-responsive miR-33-5p promotes chondrocyte senescence and osteoarthritis progression by targeting SIRT6.
Osteoarthritis (OA) is a prevalent disease among elderly individuals that is caused by cartilage degeneration. Chondrocyte senescence involved in the development of OA, and antisenescence therapies have been proposed for OA treatment. In our study, we identified the role of a microRNA, miR-33-5p, in promoting chondrocyte senescence and OA progression. miR-33-5p expression was upregulated under senescence conditions. miR-33-5p-mimic transfection can induce cellular senescence, while transfection of a miR-33-5p-inhibitor in chondrocytes alleviated senescence induced by IL-1β. Moreover, SIRT6 expression was downregulated under IL-1β treatment, and could be restored by miR-33-5p-inhibitor transfection. Luciferase assays revealed that miR-33-5p targeted the SIRT6 mRNA 3' UTR. In addition, SIRT6 mRNA expression showed negative correlations with senescence and OA degree in human cartilage. Bioinformatic analysis also confirmed the pro-senescence effect of miR-33-5p. Furthermore, periodic intraarticular injection of agomiR-33-5p induced cartilage loss and OA-like cartilage changes. To conclude, we revealed the pro-senescence and cartilage-destructive effect of miR-33-5p, whose expression was elevated under various senescence conditions, and showed that SIRT6 was one of its targets. Therefore, miR-33-5p is a potential therapeutic target for treating OA.


Tryptophan hydroxylase and serotonin receptor 1A expression in the retina of the sea lamprey.
The dual development of the retina of lampreys is exceptional among vertebrates and offers an interesting EvoDevo (evolutionary developmental biology) model for understanding the origin and evolution of the vertebrate retina. Only a single type of photoreceptor, ganglion cell and bipolar cell are present in the early-differentiated central retina of lamprey prolarvae. A lateral retina appears later in medium-sized larvae (about 3 years after hatching in the sea lamprey), growing and remaining largely neuroblastic until metamorphosis. In this lateral retina, only ganglion cells and optic fibers differentiate in larvae, whereas differentiation of amacrine, horizontal, photoreceptor and bipolar cells mainly takes place during metamorphosis, which gives rise to the adult retina. Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter found in the retina of vertebrates whose synthesis is mediated by the rate-limiting enzyme tryptophan hydroxylase (TPH). TPH is also the first enzyme in the biosynthetic pathways of melatonin in photoreceptor cells. The serotonin 1A receptor (5-HT1A) is a major determinant of the activity of both serotonergic cells and their targets due to its pre- and post-synaptic location. Here, we report the developmental pattern of expression of tph and 5-ht1a transcripts in the sea lamprey retina by means of in situ hybridization. In larvae, strong tph mRNA signal was observed in photoreceptors and putative ganglion cells of the central retina, and in some neuroblasts of the lateral retina. In adults, strong tph expression was observed in bipolar, amacrine and ganglion cells and in photoreceptors. In the prolarval (central) retina, all the differentiated retinal cells expressed 5-ht1a transcripts, which were not observed in undifferentiated cells. In larvae, photoreceptors, bipolar cells and ganglion cells in the central retina, and neuroblasts in the lateral retina, showed 5-ht1a expression. In the adult retina, expression of 5-ht1a transcript was mainly observed in the myoid region of both short and long photoreceptors, and was also observed in bipolar, amacrine and ganglion cells. Some 5-HT-immunoreactive amacrine cells have already been reported in the adult lamprey retina. Our study supports the serotonergic phenotype of these amacrine cells of lampreys and also suggests that other retinal neurons could synthesize serotonin at levels not detectable by immunohistochemistry. The expression of the tph transcript in retinal photoreceptors of lampreys strongly suggests that they synthesize melatonin and that this pathway appeared early and has been conserved throughout evolution in vertebrates. The expression of tph and 5-ht1a in neuroblasts also indicates that serotonin might be playing developmental roles in the larval lamprey retina.


Endometrial biopsy during treatment of luteal phase defects is predictive of therapeutic outcome.
Luteal phase deficiency (LPD), as diagnosed by endometrial biopsy, is not a single disorder but rather a spectrum of dysfunction that reflects both endometrial cycle and ovarian cycle abnormalities. Forty-three patients were diagnosed as having LPD by two consecutive abnormal cycles. Seven patients (16%) with hyperprolactinemia received bromocriptine, and one hypothyroid patient received thyroid replacement. The remaining patients were treated sequentially with progesterone suppositories, clomiphene, the combination, and follicle-stimulating hormone and luteinizing hormone. If no conception occurred in 6 months on a given type of therapy, treatment was advanced. Patients were rebiopsied on each medication. In all, 33 of 41 (81%) compliant patients conceived. No viable pregnancies occurred without normal endometrial maturation, regardless of the treatment modality employed. When compared with time-life table projections, pregnancies occurred at rates comparable to those of a normal population once normal endometrial maturation was obtained with therapy. The endometrial biopsy accurately reflects the functional state of both the ovarian cycle and the endometrial cycle and can be used to determine adequacy of therapy, thereby improving conception rates in patients with LPD and eliminating the need for therapeutic trials.


Diethyl 4-(1H-imidazol-2-yl)-2,6-dimethyl-1,4-di-hydro-pyridine-3,5-di-carboxyl-ate.
In the title compound, C16H21N3O4, the 1,4-di-hydro-pyridine ring adopts a flattened boat conformation, with the imidazole substituent in an axial orientation [dihedral angle between ring planes = 82.9 (6)°]. In the crystal structure, pairs of N-H⋯O and N-H⋯N hydrogen bonds with graph-set notation R 2 2(14) connect the mol-ecules into chains running along the c-axis direction.


Role of CXCR2 on the immune modulating activity of α-iso-cubebenol a natural compound isolated from the Schisandra chinensis fruit.
Previously, we demonstrated that α-iso-cubebenol, a natural compound isolated from the fruits of Schisandra chinensis, strongly enhances therapeutic efficacy against cecal ligation and puncture challenge-induced sepsis. In this study, we found that α-iso-cubebenol stimulated calcium increase and degranulation in human neutrophils. α-Iso-cubebenol also strongly induced neutrophil chemotaxis, which was completely blocked by a CXCR2 antagonist, SB225002. The increased survival rate by α-iso-cubebenol was also significantly attenuated by SB225002. Taken together, the results indicate that α-iso-cubebenol-induced anti-septic activity was mediated by CXCR2, suggesting CXCR2 as an important target for the regulation of sepsis and inflammation.


Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain.
The cannabinoid receptor type 1 (CB1) displays unusual properties, including the dual capacity to inhibit or stimulate adenylate cyclase and a brain density considerably higher than the majority of G protein-coupled receptors. Together with overlapping expression patterns of dopamine and serotonin receptors this suggests a potential of CB1 to modulate the function of the dopamine and serotonin system. Indeed, pharmacological studies provide evidence for cross-talks between CB1 and receptors of these neurotransmitter systems. In trying to obtain further insights into possible functional and/or structural interactions between CB1 and the dopamine receptors and the serotonin receptors, we performed double-label in situ hybridization at the cellular level on mouse forebrain sections by combining a digoxigenin-labelled riboprobe for CB1 with 35S-labelled riboprobes for dopamine receptors D1 and D2, and for serotonin receptors 5-HT1B and 5-HT3, respectively. As a general rule, we found that CB1 colocalizes with D1, D2 and 5-HT1B only in low-CB1-expressing cells which are principal projecting neurons, whereas CB1 coexpression with 5-HT3 was also observed in high-CB1-expressing cells which are considered to be mostly GABAergic. In striatum and olfactory tubercle, CB1 is coexpressed to a high extent with D1, D2 and 5-HT1B. Throughout the hippocampal formation, CB1 is coexpressed with D2, 5-HT1B and 5-HT3. In the neocortex, coexpression was detected only with 5-HT1B and 5-HT3. In summary a distinct pattern is emerging for the cannabinoid system with regard to its colocalization with dopamine and serotonin receptors and, therefore, it is likely that different mechanisms underlie its cross-talk with these neurotransmitter systems.


Rb(+)/Cs(+) selectivity of benzo and tribenzo derivatives of the 21C7 crown ether. A density functional study.
A density functional study has been performed on Rb(+) and Cs(+) complexes of mono and tribenzo derivatives of the 21Crown7 crown ether. Calculations have been carried out using the B3LYP functional together with a split valence basis set with additional polarization and diffuse functions. The cations have been described with effective core potentials. Structures of the tribenzo-21Crown7 are compared to X-ray data. The Rb(+)/Cs(+) affinity of the benzo and tribenzo derivatives in gas phase is discussed on the basis of binding energies, strain energies, and electrostatic contributions. For the first time, a detailed description of the effect arising from the presence of benzo groups is described. On one hand, the benzo groups decrease the electronic density on the ether oxygen atoms. On the other hand, they confer a stronger electronic polarizability to the ligand. The energetic analysis shows that the polarization contributions play a crucial role and reach up to 29% of the total electrostatic energy.


Control of swing movement: influences of differently shaped substrate.
Stick insects were studied while walking on different substrates. The trajectories of swing movements are recorded. The starting position of a swing movement is varied in vertical direction and in the direction parallel to body long axis. The trajectories found cannot be predicted by an ANN (Swingnet1) proposed earlier to describe swing movements. However, a modified network (Swingnet2) allows for a satisfying description of the behavioral results. Walking on a narrow treadwheel leads to different swing trajectories compared to walking on a broad treadwheel. These trajectories cannot be described by Swingnet1, too. The form of the swing trajectory may depend on the direction of the force vector by which the leg acts on the ground in the preceding stance. Based on this assumption, an alternative hypothesis (Swingnet3) is proposed that can quantitatively describe all results of our experiment. When stick insects walk from a wide to a narrow substrate, transition between different swing trajectories does not change gradually over time. Rather, the form of the trajectory is determined by the current sensory input of the leg on a step-to-step basis. Finally, four different avoidance reflexes and their implementation into swing movements are investigated and described by a quantitative simulation.


Male rats exposed to cocaine in utero demonstrate elevated expression of Fos in the prefrontal cortex in response to environment.
Prenatal cocaine exposure has been associated with disruption in attention and short-term memory in exposed children and in animal models. The biochemical change or changes responsible for these cognitive deficits are not known. An intriguing possibility, however, is that cocaine exposure during development disrupts the morphology or function of the frontal cortex, a region thought to contribute to cognitive and executive functions. In this report, we examined the effects of intravenous prenatal cocaine exposure on the expression of the immediate-early gene, c-fos, in the adolescent offspring to determine potential sites of disruption. The expression of Fos protein was similar in unhandled rats prenatally treated with saline or cocaine. Prenatal cocaine exposed rats that were handled, but not footshocked, however, demonstrated a dramatic selective increase in Fos expression in the ventral and medial prefrontal cortex. A footshock-induced increase in Fos expression in the prefrontal cortex was noted in prenatal saline, but not prenatal cocaine rats. Interestingly, no differences were noted in baseline or footshock-induced increased Fos expression in nuclei of the amygdala in prenatal cocaine and prenatal saline rats, indicating some aspect of the central response to stress appear unchanged. The unusual activation of the neurons of the medial and ventral prefrontal cortex may be a consequence of in utero cocaine exposure that contributes to the reported deficit in cognition.


Role of VEGF in maintaining renal structure and function under normotensive and hypertensive conditions.
Inhibiting the actions of VEGF is a new therapeutic paradigm in cancer management with antiangiogenic therapy also under intensive investigation in a range of nonmalignant diseases characterized by pathological angiogenesis. However, the effects of VEGF inhibition on organs that constitutively express it in adulthood, such as the kidney, are mostly unknown. Accordingly, we examined the effect of VEGF inhibition on renal structure and function under physiological conditions and in the setting of the common renal stressors: hypertension and activation of the renin-angiotensin system. When compared with normotensive Sprague-Dawley (SD) rats, glomerular VEGF mRNA was increased 2-fold in transgenic (mRen-2)27 rats that overexpress renin with spontaneously hypertensive rat (SHR) kidneys showing VEGF expression levels that were intermediate between them. Administration of either an orally active inhibitor of the type 2 VEGF receptor (VEGFR-2) tyrosine kinase or a VEGF neutralizing antibody to TGR(mRen-2)27 rats resulted in loss of glomerular endothelial cells and transformation to a malignant hypertensive phenotype with severe glomerulosclerosis. VEGFR-2 kinase inhibition treatment was well tolerated in SDs and SHRs; although even in these animals there was detectable endothelial cell loss and rise in albuminuria. Mild mesangial expansion was also noted in hypertensive SHR, but not in SD rats. These studies illustrate: (i) VEGF has a role in the maintenance of glomerular endothelial integrity under physiological circumstances, (ii) glomerular VEGF is increased in response to hypertension and activation of the renin-angiotensin system, and (iii) VEGF signaling plays a protective role in the setting of these renal stressors.


Ready for flu season? The 2011-2012 ACIP recommendations.
Strains in this year's vaccine are identical to last year's, but revaccination is strongly recommended. Also, the dosing decision for children < 9 years has been simplified.


Prediction of fetal birthweight in Taiwanese women with pre-eclampsia and gestational hypertension using an equation based on maternal characteristics.
The purpose of the present study was to develop a method for predicting the birthweight of newborns in women with pre-eclampsia and gestational hypertension based on maternal characteristics and pregnancy-related factors. A total of 661 consecutive pregnant women with pre-eclampsia and gestational hypertension who delivered at Chang Gung Memorial Hospital from 1994 to 2003 were included in the analysis. Multivariate regression formulas (Models I and II) were derived from maternal characteristics to predict low infant birthweight. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated and tested for these formulas. The Model I formula was as follows: Using a cut-off value of 2210 g, the equation predicts the occurrence of a low birthweight baby with 90.9% sensitivity. If higher specificity is required, increasing the cut-off value to 2488 g yields a specificity of 95.2%. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 93.7 (95% confidence interval [CI], 0.88 to 0.99) for low birthweight baby prediction in Model I. The results suggest that these regression formulas based on maternal characteristics may accurately predict low birthweight babies in pregnant women with pre-eclampsia and gestational hypertension. The cut-off values were determined and cross-validated by ROC curve analysis.


Oligodendrocyte-specific deletion of Xbp1 exacerbates the endoplasmic reticulum stress response and restricts locomotor recovery after thoracic spinal cord injury.
The endoplasmic reticulum stress response (ERSR) is activated in various neurodegenerative diseases and/or after CNS traumatic injuries. The ERSR is comprised of three major arms, PERK, IRE-1, and activating transcription factor-6, with the latter two contributing to the unfolded protein response (UPR). PERK activity overlaps with the integrated stress response (ISR) kinases, PKR, HRI, and GCN2 which all signal through, eukaryotic initiation factor 2α, ATF4, and CHOP. All initially attempt to restore endoplasmic reticulum (ER) homeostasis, but if ER stress is unresolved, ATF4/CHOP-mediated cell death is initiated. Here, we investigate the contribution of the inositol-requiring protein-1α-X-box binding protein-1 (XBP1)-mediated UPR signaling pathway to the pathogenesis of spinal cord injury (SCI). We demonstrate that deletion of Xbp1 caused an exacerbated ATF4/CHOP signaling in cultured mouse oligodendrocyte (OL) progenitor cells and enhanced their sensitivity to ER stress. Similar effects were also observed with the Xbp1 pathway inhibitor toyocamycin. Furthermore, OL lineage-specific loss of Xbp1 resulted in enhanced ISR in mice that underwent moderate contusive SCI at the T9 level. Consistently, post-injury recovery of hindlimb locomotion and white matter sparing were reduced in OL Xbp1-deficient mice, which correlated with chronically decreased relative density of OPCs and OLs at the injury epicenter at 6 weeks post-SCI. We conclude that the IRE1-XBP1-mediated UPR signaling pathway contributes to restoration of ER homeostasis in OLs and is necessary for enhanced white matter sparing and functional recovery post-SCI.


Correction to: Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease.
The original version of this article contained an error in one of the author name. The co-author name was published as "Elliot Fishman", instead it should be "Elliot K. Fishman". The original article has been corrected.


Inhibition of the formation of myotubes in vitro by inhibitors of transglutaminase.
The effects of competitive inhibitors of transglutaminase on the formation of myotubes by the fusion of myoblasts in vitro has been investigated. Myotube formation was inhibited when myoblasts from 11-day-old chick embryos were cultured in vitro in the presence of 10 mM histamine or 0.2 mM dansyl cadaverine. The inhibitions observed were reversed when the treated cells were subsequently cultured in normal medium. Glycine methyl ester also inhibited myotube formation but sarcosine methyl ester, which is not a competitive inhibitor of transglutaminase, had little if any inhibitory action. The formation of myotubes was not inhibited by cultivation in normal medium adjusted to pH 8.0-8.1, indicating that the observed effects of histamine and of dansyl cadaverine were not mediated by a lysosomotropic effect. Inhibition of myotube formation in the presence of histamine was accompanied by the production of abnormal multinucleated cells, indicating that myoblast fusion occurred in the treated cultures but that the fused cells failed to elongate into normal myotubes. Transglutaminase activity has been found in cell-free lysates of embryonic chick myoblasts and it is concluded that a transglutaminase enzyme, activated by an increase in the concentration of intracellular Ca2+, plays an important role in stabilising the cytoskeletal network of developing myotubes.


Planarian mitochondria. II. The unique genetic code as deduced from cytochrome c oxidase subunit I gene sequences.
The cytochrome c oxidase subunit I (COI) gene sequences from planarian (Dugesia japonica) DNA, most probably of mitochondrial origin, are heterogeneous. Taking advantage of the heterogeneity that occurs primarily in silent sites of the COI DNA sequences, amino acid assignments of several codons have been deduced as nonuniversal: UGA = Trp, AAA = Asp, and AGR (R: A or G) = Ser. In addition, UAA, a stop codon in the universal genetic code, is tentatively assumed to be a tyrosine codon, because three of the sequences examined have UAA at the well-conserved tyrosine site of UAY (Y: U or C) in other planarian sequences as well as in the mitochondria of human, Xenopus, sea urchin, Drosophila, Trypanosoma, and Saccharomyces cerevisiae. AUA would most probably be an isoleucine codon in these mitochondria, whereas it is a methionine codon in the majority of nonplant mitochondria.


[Chemical peel treatments in dermatology].
Chemical peel treatments, which utilize a number of chemical peeling solutions subject to patient indication, are an easy to learn therapeutic technique suited for, in particular, various types of acne, acne scars, actinic keratosis and "sun-damaged skin". Especially the positive and long-lasting results of deep peels in the area of skin rejuvenation are deemed the gold standard against which other techniques, including lasers, must compare themselves. Other benefits of chemical peels include the flexibility to mix and match chemical solutions to custom design the treatment best suited for the desired degree of skin penetration, as well as the relatively low cost.


Revealing tumor microstructure with oscillating diffusion encoding MRI in pre-surgical and post-treatment glioma patients.
We hypothesized that the time-dependent diffusivity at short diffusion times, as measured by oscillating gradient spin echo (OGSE) diffusion MRI, can characterize tissue microstructures in glioma patients. Five adult patients with known diffuse glioma, including two pre-surgical and three with new enhancing lesions after treatment for high-grade glioma, were scanned in an ultra-high-performance gradient 3.0T MRI system. OGSE diffusion MRI at 30-100 Hz and pulsed gradient spin echo diffusion imaging (approximated as 0 Hz) were obtained. The ADC and trace-diffusion-weighted image at each acquired frequency were calculated, that is, ADC (f) and TraceDWI (f). In pre-surgical patients, biopsy-confirmed solid enhancing tumor in a high-grade glioblastoma showed higher ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and lower TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\ (f)}{\mathrm{TraceDWI}\ \left(0\ \mathrm{Hz}\right)} $$ , compared to that at same OGSE frequency in a low-grade astrocytoma. In post-treatment patients, the enhancing lesions of two patients who were diagnosed with tumor progression contained more voxels with high ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and low TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\left(\mathrm{f}\right)}{\mathrm{TraceDWI}\left(0\ \mathrm{Hz}\right)} $$ , compared to the enhancing lesions of a patient who was diagnosed with treatment effect. Non-enhancing T2 signal abnormality lesions in both the pre-surgical high-grade glioblastoma and post-treatment tumor progressions showed regions with high ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and low TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\ \left(\mathrm{f}\right)}{\mathrm{TraceDWI}\ \left(0\ \mathrm{Hz}\right)} $$ , consistent with infiltrative tumor. The solid tumor of the glioblastoma, the enhancing lesions of post-treatment tumor progressions, and the suspected infiltrative tumors showed high diffusion time-dependency from 30 to 100 Hz, consistent with high intra-tumoral volume fraction (cellular density). Different characteristics of OGSE-based time-dependent diffusivity can reveal heterogenous tissue microstructures that indicate cellular density in glioma patients.


Being away from home for cancer treatment: a qualitative study of patient experience and supportive care needs during radiation therapy.
Supportive care needs (SCN) refer to support required by patients and their families to better cope with cancer. Many rural radiation therapy (RT) patients stay away from home for significant periods, which can lead to the negative effects of both social isolation and cultural disparity. They may demonstrate complex SCN. This study aimed to explore experiences of being away from home by considering patient perspectives of their own SCN. The objectives were to provide a deeper understanding of how these patients think and feel and present a foundation of patient-centred insights for further research. Thirteen patients participated in semi-structured interviews; all stayed away from home for RT at the North Coast Cancer Institute for >3 days a week for >3 weeks. The data were subject to interpretive phenomenological analysis: a thorough process of understanding and analysis that is accompanied by reflection to improve researcher transparency. Two themes influenced patient experiences of their care: values and identity, and expectations. Patients discussed the value they place on rural life, community connections and health care and referred to information for managing expectations. SCN discussed fell into practical, physical and psycho-social needs. Experiences of culturally appropriate patient-centred supportive care improve control and confidence. Patient well-being is influenced by compassionate, caring and respectful connections with others. Several practical ways of managing expectations and promoting the psycho-social well-being of patients are discussed, for example, tailored packing lists and easy access to green spaces. Future research can be shaped by lived experiences.


The value of ablating oto-rhino-laryngological (ORL) foci before haematopoietic stem cell transplantation (HSCT).
Between June 1996 and May 1997, 92 patients underwent haematopoietic stem cell transplantation (HSCT) for haematological malignancies. To participate in a prospective single-centre trial to evaluate oto-rhino-laryngological (ORL) related problems, 43 of these patients (27 male, 16 female, median age 38) signed an informed consent. A questionnaire about ORL related problems was assessed before and after HSCT. Only 21 of the patients (49%) could be fully examined after transplantation because of overall mortality and follow-up realised by other health care centres. In the deceased patients, however, a close review of the patients' notes was carried out. An ORL focus was not identified as the cause of death in any of the deceased. Pre-transplant examination revealed 15 patients with ORL relevant infectious foci. To make urgent HSCT possible, surgical pre-transplant ablation of chronic ORL infection sites took place in four patients only. In this cohort, pre-transplant ORL pathology was not amplified after HSCT. None of the 11 patients presenting ORL foci before transplantation experienced enhancement of ORL disease. These data suggest that the indication for surgical intervention with regards to ORL infection prior to HSCT should be regarded cautiously. However, the potential risk of dissemination of a pre-existing fungal infection from an ORL site should be considered and treated on a case-by-case basis.


Wide-range continuous tuning of the thermal conductivity of La0.5Sr0.5CoO3-δ films via room-temperature ion-gel gating.
Solid-state control of the thermal conductivity of materials is of exceptional interest for novel devices such as thermal diodes and switches. Here, we demonstrate the ability to continuously tune the thermal conductivity of nanoscale films of La0.5Sr0.5CoO3-δ (LSCO) by a factor of over 5, via a room-temperature electrolyte-gate-induced non-volatile topotactic phase transformation from perovskite (with δ ≈ 0.1) to an oxygen-vacancy-ordered brownmillerite phase (with δ = 0.5), accompanied by a metal-insulator transition. Combining time-domain thermoreflectance and electronic transport measurements, model analyses based on molecular dynamics and Boltzmann transport equation, and structural characterization by X-ray diffraction, we uncover and deconvolve the effects of these transitions on heat carriers, including electrons and lattice vibrations. The wide-range continuous tunability of LSCO thermal conductivity enabled by low-voltage (below 4 V) room-temperature electrolyte gating opens the door to non-volatile dynamic control of thermal transport in perovskite-based functional materials, for thermal regulation and management in device applications.


An air-locking port and high-flow nasal cannula in non-intubated uniportal video-assisted thoracic surgery for pneumothorax with pulmonary dysfunction: a case report.
Non-intubated video-assisted thoracic surgery is a therapeutic option for intractable secondary spontaneous pneumothorax in patients who are poor candidates for surgery with endotracheal intubation under general anesthesia. However, intraoperative respiratory management in this surgery is often challenging because of hypoxia caused by surgical pneumothorax. A 75-year-old man with idiopathic pulmonary fibrosis who had been on home oxygen therapy underwent non-intubated uniportal video-assisted thoracic surgery for intractable spontaneous pneumothorax. During the operation, oxygen was administered using a high-flow nasal cannula at a high flow rate. An air-locking port for single-incision surgery was used to minimize the inflow of air into the pleural cavity. The intrapleural air was continuously suctioned through the chest tube. The air-leak point was easily identified and closed using ligation. Oxygenation was satisfactory throughout the operation. Non-intubated uniportal video-assisted thoracic surgery for secondary spontaneous pneumothorax with an air-locking port, continuous pleural suction, and high-flow nasal cannula may achieve satisfactory intraoperative oxygenation in patients with respiratory dysfunction. The intrapleural space can be feasible for surgical manipulation without surgical pneumothorax in non-intubated video-assisted thoracic surgery even when supplied with oxygen at a high flow rate using a high-flow nasal cannula.


Anatomical Outcomes Based on Suturing Technique During Vaginal Mesh Attachment in Robotic Sacrocolpopexy.
In this study, we assessed the difference in anatomical outcomes using the barbed, self-anchoring, delayed absorbable suture when compared with the traditional knot-tying interrupted suture technique during vaginal mesh attachment in robotic sacrocolpopexy. In addition, we compared the rates of mesh erosion with the 2 techniques. This is a retrospective cohort study of 131 women who underwent minimally invasive robotic sacrocolpopexy at 2 sites. There were 65 subjects at site 1 (barbed, self-anchoring, delayed absorbable suture) and 66 from site 2 (traditional knot-tying technique). The primary outcome was anatomical success (measured by all Pelvic Organ Prolapse Quantification System points <0 postsurgery) in the barbed suture technique at site 1 compared with the traditional knot-tying technique at site 2. The secondary outcome was mesh erosion rates at these sites. In the barbed suture group, performed at site 1, 98% (n = 59/60) had postoperative success at the 3-month follow-up period compared with 62% (n = 40/65) in the traditional knot-tying group at site 2 during the 12-month postoperative follow-up (P < 0.0001). During this time period, 2% (n = 1) in the barbed suture group and 8% (n = 5) in the traditional knot-tying group experienced sacrocolpopexy mesh erosion (P = 0.208). Our results indicate that the barbed, self-anchoring, delayed absorbable suture is associated with less anatomical failures compared with traditional knot tying. The use of barbed suture is a safe technique and can be adopted in place of the traditional knot-tying technique. We also found less mesh erosion in the barbed suture group.


Atypical male and female presentations of FLNA-related periventricular nodular heterotopia.
Periventricular nodular heterotopia, the most common form of cortical malformation in adulthood, is characterized by nodules of neurons ectopically placed along the lateral ventricles. Classically, ectopic nodules are bilateral and symmetric defining bilateral periventricular nodular heterotopia (BPNH). BPNH can lead to epilepsy and intellectual disability of variable severity. The X-linked dominant form of BPNH, related to mutations in FLNA encoding filamin A, is the major cause of BPNH, causing prenatal and neonatal lethality in males that explain the excess of affected women. However, few living males have been described with this condition. In addition, mutations in FLNA have been also exceptionally associated with unilateral nodular heterotopia. We describe here three new patients, all carrying a novel missense mutation in FLNA. Two of the patients were adult males with BPNH; both had normal cognitive development and one did not manifest any seizure until he died at age 57. The last patient was a female adult with epilepsy and focal nodules essentially located along the right ventricle. We compare the clinical and imaging data of our patients with those of previously described similar cases. The type and location of FLNA mutations leading to such atypical presentations are discussed.


Current status and perspectives of the development of dental research in biological anthropology of Argentina: introduction and conclusions of the symposium.
This paper describes and discusses the research in the field of dental anthropology in Argentina. It has been presented at the symposium entitled "The development of dental research in Argentine Biological Anthropology: current status and perspectives", coordinated by the authors at the IX National Meeting of Biological Anthropology of Argentina, Puerto Madryn, 20th-23rd October 2009. The aim of the symposium was to present new results and future prospects of this discipline in the country and to create a forum for discussion of current research within this field. Six contributions that focused on the study of teeth from different perspectives and analysed bioarchaeological samples from different areas of Argentina (Central Highlands, Pampa and Patagonia) were presented. After the presentations, a discussion about the state of the art of dental research in the country was generated, in which the need for the generation of methodological consensus on the criteria for the evaluation of the variables considered was stated, so that research conducted in different areas can be compared. In short, the contributions of this symposium provide insights into the diversity of dental anthropology in contemporary Argentina and the potential of these types of studies to gain important information about biological and cultural aspects of the native populations in the country.


Message received: Concordance between parents and children in perceptions of messages about race and ethnic identity development.
The objective of this study was to examine the agreement between African American and Latinx parents and their school-age children regarding the amount of ethnic-racial socialization (ERS) parents provided and relations to youth ethnic-racial identity development. The sample included 353 parents and their 10-11 year-old children (57% Latinx; 55% boys), who both completed surveys 1 year apart. Latent difference scores were used to quantify agreement between parents and youth and to examine the relation between agreement and family and child characteristics including youth ethnic-racial identity development. Parents reported higher levels of ERS than children, and differences were greater for preparation for bias than cultural socialization. Higher levels of cultural socialization and greater discrepancies between parent and youth reports were associated with greater ethnic-racial identity development 1 year later. Greater discrepancies in report of bias preparation were associated with less ethnic-racial identity development, but this effect was not significant once the impact of parent-reported bias preparation was accounted for. Incorporating both parent and youth reports of ERS provides a more complete picture of these practices and associated outcomes. Implications for the study of ERS and clinical intervention are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Low diastolic wall strain is associated with raised post-exercise E/E' ratio in elderly patients without obvious myocardial ischemia.
It has been reported that the diastolic wall strain (DWS) inversely correlates with the myocardial stiffness constant. The ratio of early diastolic transmitral flow velocity to annulus velocity (E/E') correlates with the left ventricular (LV) filling pressure. Increased LV wall stiffness is thought be associated with increased LV filling pressure after exercise. The purpose of this study was to evaluate the correlation between the DWS and post-exercise E/E' in elderly patients without obvious myocardial ischemia. Fifty-eight elderly patients (age = 74 ± 6 years) who underwent treadmill stress echocardiography were studied. All patients had normal LV wall motion at rest, and patients with exercise-induced wall motion abnormality were excluded. The DWS was calculated as follows: DWS = (PWTs - PWTd)/PWTs, where PWTs is the LV posterior wall thickness at end-systole and PWTd is that at end-diastole. As previously reported, DWS ≤ 0.33 was defined as low DWS and E/E' ≥15.0 was defined as a marker of increased LV filling pressure. Eighteen patients had low DWS. Patients with low DWS had greater post-exercise E/E' (17.9 ± 3.2 vs. 12.8 ± 3.3, p < 0.0001). The DWS was inversely and strongly correlated with post-exercise E/E' (r (2) = 0.534, p < 0.0001). Low DWS predicted the development of raised post-exercise E/E' ≥15.0 with a positive predictive value of 94 % and a negative predictive value of 85 %. In elderly patients without obvious myocardial ischemia, the DWS correlates strongly and inversely with post-exercise E/E'. Patients with low DWS were likely to develop raised E/E' after exercise.


Immunoglobulin replacement therapy in children.
The benefit of immunoglobulin (IG) replacement in primary antibody deficiencies is unquestionable. Many of these congenital disorders present early in life and this therapy is often first implemented in the young. This article focuses on the indications of IG replacement in children, with an emphasis on the specific diagnostic problems encountered in this population. Also presented is an overview of the practical aspects of IG administration in the pediatric setting, including the recognition and management of adverse reactions. Finally, the advent of subcutaneous IG, a therapeutic IG modality with the potential to have a great impact on the quality of life of children with antibody deficiencies and their families, is discussed.


Moxonidine into the lateral parabrachial nucleus reduces renal and hormonal responses to cell dehydration.
The deactivation of the inhibitory mechanisms with injections of moxonidine (α2-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 μl) into the LPBN decreased i.g. 2 M NaCl-induced diuresis (4.6±0.7 vs. vehicle: 7.4±0.6 ml/120 min) and natriuresis (1.65±0.29 vs. vehicle: 2.53±0.17 mEq/120 min), whereas the previous injection of the α2-adrenoceptor antagonist RX 821002 (10 nmol/0.2 μl) into the LPBN abolished the effects of moxonidine. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6±2.8 and 2.2±0.3 vs. vehicle: 25.7±7 and 4.3±0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5±1.7 vs. vehicle: 0.5±0.2 mEq/2 h) and produced positive sodium balance (2.3±1.4 vs. vehicle: -1.2±0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN α2-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion.


Immunocytochemical demonstration of mammalian lutropin-like material in the pituitary of the lungfish, Lepidosiren paradoxa.
The presence of lutropin (LH)-like material in the pituitary gland of the South-American lungfish, Lepidosiren paradoxa, has been demonstrated by means of the unlabeled antibody-enzyme method, by use of rabbit anti-ovine LH as first antibody. The LH-like substance was revealed in a single PAS-positive cell type primarily located in the anterior part of the distal lobe. Dot blot tests as well as conventional liquid-phase absorption experiments indicate that the anti-ovine LH antibodies possess specificity against the oLH beta subunit. These observations indicate that dipnoans (Lepidosiren) share a number of antigenic determinants with those of mammalian LH beta and support the concept that mammalian LH beta, or part of it, was established early in evolution. The exact nature and physiological function of the substance detected remains to be defined.


The effect of sera from patients with connective tissue diseases on red cell binding and phagocytosis by monocytes.
The uptake by human blood monocytes of sheep erythrocytes treated with rabbit anti-sheep antibody with or without mouse complement was assessed by a radioactive method to discover whether immune complexes would inhibit this reaction. It was found that sera from SLE patients inhibited uptake whereas normal sera enhanced. Some rheumatoid sera and rheumatoid joint fluids inhibited uptake whereas sera from juvenile rheumatoid patients did not.


A comparison of ThinPrep against four non-volatile transport media for HPV testing at or near the point of care.
The Xpert HPV Test is used at point of care for cervical screening in a number of low and middle income countries (LMIC). It is validated for use with ThinPrep-PreservCyt transport medium which has a high methanol content and is therefore classified as a dangerous good for shipping, making cost, transportation and use challenging within LMIC. We compared the performance of ThinPrep against four non-volatile commercially available media for human papillomavirus (HPV) point of care testing. Ten-fold serial dilutions were prepared using three HPV cell lines each positive for 16, 18 or 31 and with each suspended in five different media types. The media types consisted of Phosphate Buffered Saline (ThermoFisher Scientific, USA), Sigma Virocult (Medical Wire and Equipment, UK), MSwab (Copan, Italy) Xpert Transport Media (Cepheid, USA) and ThinPrep-PreservCyt (Hologic, USA). A total of 105 Xpert HPV tests were conducted in a laboratory setting, with seven 10-fold dilutions of each of the three HPV genotypes tested in all five media types. The lowest HPV 10-fold dilution detected for any media, or cell line was the fifth dilution. MSwab was the only medium to detect HPV to the fifth dilution across all three cell types. MSwab transport media may be a suitable alternative to ThinPrep for Xpert HPV point of care testing. A field based, head to head comparison of both media types using the Xpert HPV assay is warranted to confirm these laboratory based findings.


Anti-inflammatory drugs in the prevention of post-operative atrial fibrillation: a literature review.
Atrial fibrillation (AF) is a serious and common complication following heart surgery. Cardiac surgery triggers inflammation in the heart and makes it susceptible to the incidence of AF. Therefore, anti-inflammatory drugs may reduce the rate of AF incidence in the post-surgery conditions. Immunosuppressant agents, steroidal anti-inflammatory drugs (corticosteroids), non-aspirin non-steroid anti-inflammatory drugs (NSAIDs), colchicine and omega-3 unsaturated fatty acids (n-3 UFA) are drugs with well-known anti-inflammatory properties. The efficacy, safety and other aspects of using these drugs in the prevention of post-operative AF (POAF) have been reviewed here. Studies evaluating the efficacy of colchicine have shown that it could be effective in the prevention of POAF. However, there is a need for additional studies to find a colchicine regimen with optimal efficacy and higher tolerability. The use of corticosteroids may also be of value based on the most of meta-analyses. In the case of n-3 polyunsaturated fatty acids and NSAIDs, current data fail to support their efficacy in POAF prevention. Moreover, perioperative administration of NSAIDs may be associated with some severe safety considerations. Immunosuppressant agents have not been used for the prevention of POAF. Further studies are needed to find the most effective strategy for POAF prevention with the least safety considerations and the highest health benefits.


Neurological illness in transgenic mice expressing a prion protein with an insertional mutation.
Familial prion diseases are caused by mutations in the gene encoding the prion protein (PrP). We have produced transgenic mice that express the mouse homolog of a mutant human PrP containing a nine octapeptide insertion associated with prion dementia. These mice exhibit a slowly progressive neurological disorder characterized clinically by ataxia and neuropathologically by cerebellar atrophy and granule cell loss, gliosis, and PrP deposition that is most prominent in the cerebellum and hippocampus. Mutant PrP molecules expressed in the brains of these mice are resistant to digestion by low concentrations of proteinase K and display several other biochemical properties reminiscent of PrP(Sc), the pathogenic isoform of PrP. These results establish a new transgenic animal model of an inherited human prion disorder.


Immunoglobulin diversification in bursal duct-ligated chickens.
The role of external antigen contact on immunoglobulin (Ig) diversification occurring in chicken bursal cells was evaluated. The entry of environmental antigens into the lumen of the bursa of Fabricius was prevented by ligating the bursal duct prior to hatching (BDL: bursal duct ligation). We used two-dimensional gel electrophoresis to compare the heterogeneity of Ig molecules from bursa cells of normal and BDL chickens. We have found that Ig diversity obtained from BDL chickens' bursae in two-dimensional gel analysis was similar to that of control birds. Furthermore, by using two monoclonal anti-idiotype antibodies to study intrabursal Ig diversification we have shown that frequencies of the Cld-1 and Cld-2 idiotypes were also unaltered following bursal ligation. We conclude that primary B cell diversification in the bursa is independent of the external antigen flow from the bursal lumen.


Coronary artery anomalies: A diagnostic challenge.
Coronary artery anomalies (CAAs) are found in approximately 1% of all patients undergoing coronary angiography and in 0.3% of patients undergoing autopsy (Roberts, 1986). CAAs may be classified into those of origin and course, intrinsic coronary arterial anatomy, and coronary termination (Angelini et al. 2002). The most common malformation is abnormal origin and course, origin of a coronary artery from a wrong aortic sinus of Valsalva; either the right from the left coronary sinus or the left from the right coronary sinus; these anomalies must be excluded in young adults with typically ischemic- sounding chest pain or syncope. Anomalies coronary artery termination typically presented as coronary artery fistula, commonly the right coronary artery is affected, although, left sided coronary artery fistulae are well documented (Gandy et al. 2004). The anomalies of intrinsic coronary arterial anatomy, such as ostial stenosis, Artesia, and single, absent, or hypoplastic coronary arteries are rare but may have clinical importance.


Transcatheter closure of PFO as secondary prevention of cryptogenic stroke.
This article covers the main unsolved issues regarding the potential role that the patent foramen ovale (PFO) plays in the genesis of so-called cryptogenic stroke. Some brief notions of the anatomy and epidemiology of the PFO are outlined. Subsequently, the results of the three trials on secondary prevention (medical therapy vs. transcatheter closure) in patients with PFO and a history of cryptogenic stroke are presented. The conflicting results of numerous meta-analyses derived from the three randomized controlled trials are discussed. Official scientific guidelines dispute an alleged superior efficacy of transcatheter PFO occlusion in comparison with antithrombotic therapy alone (anticoagulants or antiplatelet agents), except for selected cases of patients with documented PFO and a concomitant clinical-instrumental picture of deep venous thrombosis. Nevertheless, considering recent doubts about the presumptive thrombogenic and arrhythmogenic potential of PFO occlusion, which concerns only one of the septal occluders previously used, further in-depth investigations are warranted, centered on the use of newer dedicated devices to be tested in comparison with antithrombotic regimens alone.


Deformation of the mandible due to neonatal moulding: a 10-year follow-up.
A 3-day-old infant with paralysis of the marginal mandibular branch of the facial nerve and asymmetry of the mandible due to neonatal moulding is presented. Ten years after the initial presentation, the asymmetry and paralysis was still present. Orthodontic treatment has been instituted because of malocclusion. Surgical correction of the mandibular asymmetry after adulthood seems not to be necessary.


Lipid profiles and outcomes of patients with prior cancer and subsequent myocardial infarction or stroke.
Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007-2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85-0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91-0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37-1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52-2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer.


Variation between different samples of SITS with respect to axonal transport and toxicity.
Retrograde axonal transport of the fluorescent compound SITS has been described as occurring only from axon terminals and not from axons of passage. Injection of 4 different commercially available samples of SITS into terminations of cerebellar pathways in the rat revealed that only one sample produced retrogradely labelled neurones. Chemical analysis suggested that this was due to a unique fluorescent component (not SITS). This sample also contained other fluorescent components one of which, present in two other samples, produced paroxysmal motor disturbances. All of the samples examined contained several other fluorescent compounds.


Greater Empathic Abilities and Resting State Brain Connectivity Differences in Psychotherapists Compared to Non-psychotherapists.
In a therapeutic environment a proper regulation of the empathic response strengthens the patient-therapist relationship. Thus, it is important that psychotherapists constantly regulate their own perspective and emotions to better understand the other's affective state. We compared the empathic abilities of a group of 52 psychotherapists with a group of 92 non-psychotherapists and found psychometric differences. Psychotherapists showed greater scores in Fantasy and Perspective Taking, both cognitive empathy constructs, and lower scores in the use of expressive suppression, an emotional regulation strategy that hampers the empathic response, suggesting that psychotherapists exert top-down processes that influence their empathic response. In addition, the expected sex differences in empathic concern and expressive suppression were only present in the non-psychotherapist group. To see if such psychometric differences were related to a distinctive functional organization of brain networks, we contrasted the resting state functional connectivity of empathy-related brain regions between a group of 18 experienced psychotherapists and a group of 18 non-psychotherapists. Psychotherapists showed greater functional connectivity between the left anterior insula and the dorsomedial prefrontal cortex, and less connectivity between rostral anterior cingulate cortex and the orbito prefrontal cortex. Both associations correlated with Perspective Taking scores. Considering that the psychometric differences between groups were in the cognitive domain and that the functional connectivity associations involve areas related to cognitive regulation processes, these results suggest a relationship between the functional brain organization of psychotherapists and the cognitive regulation of their empathic response.


Effect of Certain Antibiotics Against Filarial Parasite Brugia malayi In Vitro: Possible Role of Oxidative Stress.
WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20-100 μg/ml) or ciprofloxacin (50-250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.


Recovery of subtropical coastal intertidal system prokaryotes from a destruction event and the role of extracellular polymeric substances in the presence of endocrine disrupting chemicals.
Intertidal sediments constitute the micro-environment for the co-existence of endocrine disrupting chemicals (EDCs) and biofilms consisting of the microbial community and extracellular polymeric substances (EPS). However, the interactions and the resulting eco-function of this community are complex and poorly characterized, especially after a destruction event. This study evaluates the re-construction of biofilms in terms of the abundance of prokaryotic cells and related EPS characterization in two destroyed sedimentary matrices from subtropical environments simulated by sterilization in the presence of EDCs and investigates the role of EPS. The results show that benthic prokaryotes recover from the deposition of active prokaryotes in natural seawater and form biofilms after sterilization. Sterilization triggers the release of polysaccharides and protein from lysed native microbial cells and bound EPS in sedimentary organic matter, thus increasing their concentrations. The increased portion of EPS also acts as a persistent stress on re-colonizing prokaryotes and leads to the overproduction of sedimentary EPS. Due to the protective role mediated by EPS, the effect of EDCs on biofilm composition in sterilized sediment is not significant. The sedimentary matrix is the most important determinant of the composition of the biofilm and the occurrence of EDCs. At the end of an 84-day experiment, the abundance of prokaryotic cells and the concentrations of polysaccharides and protein in mangrove sediment are 1.6-1.8 times higher than those in sandflat sediment, regardless of EDCs. Sandflat sediment exhibits higher concentrations of nonylphenol and bisphenol A but a lower concentration of 17α-ethinylestradiol than mangrove sediment. This study enhances our understanding of the role of sedimentary biofilms and the fate of EDCs in intertidal systems and highlights the benefit of a destructive event in enhancing ecosystem function, particularly tolerance to EDC adversity due to EPS production.


High nuclear poly-(ADP-ribose)-polymerase expression is prognostic of improved survival in pancreatic cancer.
Poly-(ADP-ribose)-polymerases (PARPs) act as post-translational modifiers of proteins that are mainly involved in the DNA repair machinery, and have recently been shown to be predictive of pathologically complete remission after chemotherapy in breast cancer. In the pancreas, PARP expression has so far only been studied in inflammatory conditions. Therefore, in this study, we investigated the relevance of PARP in pancreatic cancer. Cytoplasmic and nuclear PARP expression was assessed by immunohistochemistry in a population-based cohort of 178 adenocarcinomas of the pancreas and correlated with clinicopathological parameters. We found that low-level nuclear expression of PARP is associated with a poor prognosis (median survival 9.6 versus 14.5 months, P = 0.004). Our analysis shows that nuclear PARP is an independent prognostic marker with respect to standard clinicopathological parameters. These results suggest that PARP should be further explored as a predictive factor with respect to conventional chemotherapy and concepts of PARP inhibitor therapy in pancreatic cancer.


Interaction of a lymphokine with normal human macrophages results in release of a suppressor factor for mitogen-induced immunoglobulin synthesis.
Normal human macrophage/monocyte cultures exposed to a suppressor factor produced by concanavalin A-activated T cells (T-SF), respond by releasing after 72 h a macrophage-derived suppressor factor (M phi-SF). The M phi-SF inhibits pokeweed mitogen-induced Ig synthesis but not T- or B-cell proliferation. Cycloheximide treatment of the macrophages does not interfere with generation of the M phi-SF, suggesting that de novo synthesis is not required. The factor is not preformed, for virgin macrophages do not contain M phi-SF, but it appears in macrophage cell lysates after exposure to T-SF. The production of the M phi-SF is inhibited by the presence of 2-mercaptoethanol. Both T-SF and M phi-SF are L-rhamnose inhibitable, and the M phi-SF appears to be released as a high molecular weight complex which is dissociable into a low molecular weight form of a size similar to the T-SF, i.e. approximately 20,000. The T-SF induced M phi-SF has some similarities with soluble immune response suppressor (SIRS) but differs from this factor in its lack of effect upon lymphocyte proliferation failure to induce conversion of T-SF to M phi-SF by treatment with H2O2.


ASP8497 is a novel selective and competitive dipeptidyl peptidase-IV inhibitor with antihyperglycemic activity.
Dipeptidyl peptidase (DPP)-IV inhibitors are expected to become a useful new class of antidiabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of ASP8497, (2S,4S)-4-fluoro-1-({[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile monofumarate, which is a novel DPP-IV inhibitor. ASP8497 inhibited DPP-IV in plasma from mice, rats, dogs and humans with IC(50) values of 3.86, 2.36, 5.53 and 5.30 nM, respectively. In contrast, ASP8497 did not potently inhibit DPP8 or DPP9 activity (IC(50)>200 nM). Kinetic analysis indicated that ASP8497 inhibits DPP-IV activity in a competitive manner. In streptozotocin-nicotinamide-induced diabetic mice, ASP8497 (3 mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 0.5 and 8.5 h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels. In contrast, ASP8497 (3 and 30 mg/kg) did not cause hypoglycemia in fasted normal mice. Furthermore, administration of exogenous GLP-1 induced significant inhibition of gastric emptying and small intestinal transit rates, but ASP8497 (30 mg/kg) had no significant effects in normal mice. These present preclinical studies indicate that ASP8497 is a novel selective DPP-IV inhibitor with long-acting antidiabetic effect that might be a potential agent for type 2 diabetes.


Historical and recent change in extreme climate over East Asia.
This is an extended editors' commentary on the topical collection "Historical and recent change in extreme climate over East Asia", which collects a total of 15 papers related to the change and variability of extreme climate events in East Asia over the last few hundreds years. The extreme climate events are broadly classified into three categories: temperature and extreme warmth/coldness, precipitation and floods/droughts and western North Pacific typhoons. This commentary briefly summarizes the main findings presented in each paper in this topical collection, and outlines the implications of these findings for monitoring, detecting and modeling of regional climate change and for studying climate change impacts and adaptability. It also assesses the uncertainties of these studies, as well as the remaining knowledge gaps that should be filled in the future. One solid conclusion we can draw from these studies is that there was a marked decadal to multi-decadal variability of extreme climate events in East Asia in recent history, and the extreme events as observed during the last decades of the instrumental era were still within the range of natural variability except for some of those related to temperature. More severe and enduring droughts occurred in the early 20 th century or the earlier periods of history, frequently leading to great famines in northern China. Uncertainties remain in reconstructing historical extreme climate events and analyzing the early instrumental records. Further research could focus on the improvement of methodology in proxy based reconstruction of multi-decadal variations of surface air temperature and precipitation/drought, the recovery, digitization, calibration and verification of the early instrumental records, and the mechanisms of the observed multi-decadal variability of extreme climate in the region.


Understanding observational learning: an interbehavioral approach.
Observational learning is an important area in the field of psychology and behavior science more generally. Given this, it is essential that behavior analysts articulate a sound theory of how behavior change occurs through observation. This paper begins with an overview of seminal research in the area of observational learning, followed by a consideration of common behavior analytic conceptualizations of these findings. The interbehavioral perspective is then outlined, shedding light on some difficulties with the existing behavior analytic approaches. The implications of embracing the interbehavioral perspective for understanding the most complex sorts of behavior, including those involved in observational learning are considered.


Translating the brain transcriptome in neuroAIDS: from non-human primates to humans.
In the post-human genome project era, high throughput techniques to detect and computational algorithms to analyze differentially expressed genes have proven to be powerful tools for studying pathogenesis of neuroAIDS. Concurrently, discovery of non-coding RNAs and their role in development and disease has underscored the importance of examining the entire transcriptome instead of protein coding genes alone. Herein, we review the documented changes in brain RNA expression profiles in the non-human primate model of neuroAIDS (SIV infected monkeys) and compare the findings to those resulting from studies in post-mortem human samples of neuroAIDS. Differential expression of mRNAs involved in inflammation and immune response are a common finding in both monkey and human samples - even in HIV infected people on combination antiretroviral therapy, a shared set of genes is upregulated in the brains of both infected monkeys and humans: B2M, IFI44, IFIT3, MX1, STAT1. Additionally, alterations in ion channel encoding genes have been observed in the human studies. Brain miRNA profiling has also been performed, and up-regulation of two miRNAs originating from the same transcript, miR-142-3p and miR-142-5p, is common to human and monkey neuroAIDS studies. With increases in knowledge about the genome and advances in technology, unraveling alterations in the transcriptome in the SIV/monkey model will continue to enrich our knowledge about the effects of HIV on the brain.


A clinical approach to exercise tolerance testing in coronary artery disease.
Data from exercise tolerance testing should be incorporated into clinical decision making. A strategy for stratification of individual patients into high, indeterminate, and low-risk categories using Bruce protocol exercise testing is outlined. This approach will help to ensure further evaluation of high-risk individuals without excessive testing of patients having excellent long-term prognoses.


RU486 blocks effects of allopregnanolone on the response to restraint stress.
These experiments were designed to provide information about the potential involvement of progesterone receptors in the ability of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) to reduce the lordosis-inhibiting effects of restraint stress. Ovariectomized Fischer rats were hormonally primed with 10 μg estradiol benzoate and 4 mg/kg allopregnanolone or vehicle. One hour before allopregnanolone, rats were injected with the progesterone receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), or vehicle. Four hours after allopregnanolone or vehicle, sexual behavior was examined before and after a 5-min restraint stress. Lordosis behavior of rats primed only with estradiol benzoate declined after the 5 min of restraint while allopregnanolone prevented this decline. RU486 attenuated the ability of allopregnanolone to prevent the restraint-induced decline in lordosis behavior. These findings are consistent with earlier suggestions that progesterone receptors are involved in allopregnanolone's ability to reduce the effects of restraint stress.


Bowel stimulation before loop ileostomy closure to reduce postoperative ileus: a multicenter, single-blinded, randomized controlled trial.
The objective of this study was to evaluate the impact of preoperative bowel stimulation on the development of postoperative ileus (POI) after loop ileostomy closure. This was a multicenter, randomized controlled trial (NCT025596350) including adult (≥ 18 years old) patients who underwent elective loop ileostomy closure at 7 participating hospitals. Participants were randomly assigned (1:1) using a centralized computer-generated sequence with block randomization to either preoperative bowel stimulation or no stimulation (control group). Bowel stimulation consisted of 10 outpatient sessions within the 3 weeks prior to ileostomy closure and was performed by trained Enterostomal Therapy nurses. The primary outcome was POI, defined as an intolerance to oral food in the absence of clinical or radiological signs of obstruction, on or after postoperative day 3, that either (a) required nasogastric tube insertion; or (b) was associated with two of the following: nausea/vomiting, abdominal distension, or the absence of flatus. Between January 2017 and November 2020, 101 patients were randomized, and 5 patients never underwent ileostomy closure; thus, 96 patients (47 stimulated vs. 49 control) were analyzed according to a modified intention-to-treat protocol. Baseline characteristics were well balanced in both groups. The incidence of POI was lower among patients randomized to stimulation (6.4% vs. 24.5%, p = 0.034; unadjusted RR: 0.26, 95% CI 0.078-0.87). Stimulated patients also had earlier median time to first flatus (2.0 days (1.0-2.0) vs. 2.0 days (2.0-3.0), p = 0.025), were more likely to pass flatus on postoperative day 1 (46.8% vs. 22.4%, p = 0.022), and had a shorter median postoperative hospital stay (3.0 days (2.0-3.5) vs. 4.0 days (2.0-6.0), p = 0.003). Preoperative bowel stimulation via the efferent limb of the ileostomy reduced POI after elective loop ileostomy closure.


Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands.
It has been reported that intraventricular administration of the melanocortin 4 receptor (MC4-R) agonist MT II and antagonist SHU9119 alter food intake. We found that MT II and SHU9119 have extremely potent effects on feeding when injected in the paraventricular nucleus (PVN), a site where MC4-R gene expression is very high. Our finding provides direct evidence that MC4-R signaling is important in mediating food intake and that melanocortin neurons in the PVN exert a tonic inhibition of feeding behavior. Chronic disruption of this inhibitory signal is a possible explanation of the agouti-obesity syndrome.


Method for improved protein separation in human and animal sera.
A method of improved protein separation in human and animal sera on columns of diethylaminoethyl cellulose is described. The improvement in protein separation is achieved by employing suitably modified elution gradients, the construction of which is described. A comparison with other work shows that improved resolution has been achieved over shorter elution times.


Adenovirus type 5 DNA-protein complexes from formaldehyde cross-linked cells early after infection.
We report here the properties of viral DNA-protein complexes that purify with cellular chromatin following formaldehyde cross-linking of intact cells early after infection. The cross-linked viral DNA fractionated into shear-sensitive (S) and shear- resistant (R) components that were separable by sedimentation, which allowed independent characterization. The R component had the density and sedimentation properties expected for DNA-protein complexes and contained intact viral DNA. It accounted for about 50% of the viral DNA recovered at 1.5 h after infection but less than 20% by 4.5 h. The proportion of R component was independent of multiplicity of infection, even at less than one particle per cell. Viral hexon and protein VII, but not protein VI, were detected in the fractions containing the R component. These properties are consistent with those of partially uncoated virions associated with the nuclear envelope. A substantial proportion of the S component viral DNA had the same density as cellular chromatin. Protein VII was the most abundant viral protein present in gradient fractions that contained the S component. Complexes containing USF transcription factor cross-linked to the adenovirus major late promoter were detected by viral chromatin immunoprecipitation of the fractions containing S component. The S component probably contained uncoated nuclear viral DNA that assembles into early viral transcription complexes.


The influence of sodium hyaluronate, L-leucine and sodium taurocholate on the nebulization of aqueous betamethasone-17-valerate suspensions.
The purpose of this research was to evaluate the variables that are suggested to influence the adsorption of the hydrophilic hyaluronic acid (HA) onto the surface of the hydrophobic betamethasone-17-valerate (BV) particles in order to formulate a nebulizable suspension. The adsorption of HA from aqueous solutions (0.04% to 0.16%, w/v) to a fixed BV concentration (0.04%, w/v) under different experimental conditions, was investigated. The method of preparation of HA-BV suspensions involved suspending BV particles either in the hydrated HA solution (method 1) or in water followed by addition of solid HA (method 2). Other variables like the time required for the adsorption to complete and temperature at which adsorption is carried out were studied. The nebulization of the suspensions was tested via an air jet nebulizer connected to a twin stage impinger. In order to improve the nebulization behavior of the optimized suspension, L-leucine or sodium taurocholate was incorporated in increasing concentrations (0.01-0.04%, w/v). The optimized suspension, having a nebulization efficiency of 33.75%, was achieved following the adsorption of HA (0.1%, w/v) onto BV particles adopting method 2 of preparation and extending for three days at 4 degrees C. Incorporation of either l-leucine or sodium taurocholate significantly decreased the aggregate size of the optimized suspension and consequently caused significant increases in the nebulization efficiency to reach 46.87% and 56.25%, respectively.