Intracostal sutures decrease the pain of thoracotomy.
General thoracic surgeons spend much time dealing and treating patients' pain after thoracotomy. Two hundred eighty consecutive patients underwent elective thoracotomy for pulmonary resection. Patients with a history of chronic pain were excluded. One general thoracic surgeon performed all procedures. All patients had a functioning preoperative epidural, a skin incision the width of their latissimus dorsi muscle which was cut, sparing of the serratus anterior muscle, undercutting of the rib, preemptive analgesia of the intercostal nerve before rib spreading, and similar number of chest tubes and postoperative pain management. The first 140 patients had their chests closed with pericostal sutures (stitches placed on top of the fifth rib and on top of the seventh rib), and the next 140 patients had their chest closed with intracostal sutures (stitches placed on top of the fifth rib and through the small holes drilled in the bed of the sixth rib). Pain was objectified by a numeric pain score and by the McGill pain questionnaire at 2 weeks, and 1, 2, and 3 months postoperatively. There were 140 patients in each group, and the groups were matched for age, gender, race, types of pulmonary resections, number of chest tubes, number of broken ribs, length of chest tube duration, and length of hospital stay (p > 0.05 for all). The mean pain score for the pericostal group (P group) at 2 weeks, 1 month, 2 months, and 3 months postoperatively was 5.5, 3.8, 2.3, and 1.6, respectively. For the intracostal group it was 3.3, 1.7, 1.1, and 0.6, respectively (p = 0.004, p = 0.0001, p < 0.0001, and p < 0.0001, respectively). Descriptors of pain in the P group were more likely to be, hot/burning, shooting or stabbing (p < 0.003). Intracostal sutures seem to be less painful than pericostal sutures at 2 weeks, 1 month, 2 months, and 3 months after thoracotomy. The pain is less likely to be described as burning or shooting.


Associations of Prenatal Agricultural Farm Work with Fetal Overgrowth and Pregnancy Complications in State of Arizona Birth Records.
The purpose of this study is to examine fetal growth outcomes from agricultural worker households. Using Arizona 2006 to 2013 birth certificates with parental occupation, we identified N = 623,185 live births by agricultural household status. Logistic regression models estimated adjusted odds ratios (aORs) for macrosomia (>4000 g), postterm birth (>41 weeks), low birth weight (<2500 g), preterm birth (<37 weeks), large for GA, small for GA, and 5-minute APGAR (<7). Newborns of agricultural households (n = 6371) had a higher risk of macrosomia (aOR, 1.15; 95% CI, 1.05-1.26), large for GA (aOR, 1.12; 95% CI, 1.03-1.22), postterm birth (aOR, 1.20; 95% CI, 1.09-1.33), and low 5-minute APGAR (aOR, 1.39; 95% CI, 1.07-1.81), whereas low birth weight (aOR, 0.85; 95% CI, 0.76-0.96) and preterm birth (aOR, 0.82; 95% CI, 0.74-0.92) were inversely related. Having an agriculture working parent increased the likelihood of fetal overgrowth and low APGAR.


Polymyositis associated with hypothyroidism or hyperthyroidism: two cases and review of the literature.
Studies confirming a possible relationship of polymyositis within thyroid dysfunction, either hypothyroidism or hyperthyroidism, are hardly available. To define the association, identify clinical, laboratory, electromyographic, and pathologic features in polymyositis (PM) patients with hypothyroidism or hyperthyroidism, we conducted a MEDLINE and Chinese biomedicine database search to identify relevant literature published in the past 25 years. Seventeen cases were included. All patients were female (10 hypothyroidism patients, seven hyperthyroidism patients). The mean (SD) age of PM, hypothyroidism, and hyperthyroidism at diagnosis was 54.8 (16.7), 55.5 (16.5), and 32.7 years (10.2), respectively. PM diagnosis can precede or parallel hypothyroidism while PM may occur following the diagnosis of hyperthyroidism. The most common comorbidities were malignant tumors in these disorders, including thymoma, colon cancer, and thyroid cancer. Muscle weakness was described in 100% of patients. Other common manifestations included muscles' atrophy and pain, deep tendon reflexes, polyarthralgia, and dysphagia. Most patients had markedly elevated creatine kinase and the presence of anti-Sjogren's syndrome A (SSA) antibodies was also found in two cases. Malignancy associated with PM may more frequently occur in hypothyroidism than in hyperthyroidism. The abnormalities on electromyography and biopsy did not differ from those findings of PM. Therapy consisting of corticosteroids, thyroid hormone, or anti-thyroid drugs was administrated; however, poor prognosis seemed to be associated with malignant tumors as well as older age and the presence of anti-SSA antibodies. It is reasonable to suggest that those patients should be routinely evaluated for thyroid function, especially in older female and patients suffering from cancers.


Effects of food quality, particularly nitrogen concentrations, of Eucalyptus blakelyi foliage on the growth of Paropsis atomaria larvae (Coleoptera: Chrysomelidae).
Five groups of E. blakelyi seedlings were differentially fertilized to obtain a range of N concentrations from 0.8-3.0% dry wt in the foliage. Groups of P. atomaria larvae were reared from eclosion to the prepupal stage on these seedlings. The effects on larval growth and development caused by foliar concentrations of N, moisture content, and tannins and leaf toughness were measured. Pupal dry weight and development time of P. atomaria did not differ between those reared on foliage with N levels of 1.7-3.0% but there was a significant decrease in pupal weight and increase in development time for individuals fed foliage with N below this level. Larvae fed foliage with an average of 0.8% N died before reaching instar III. Total dry matter consumption increased with a decrease in N concentration. Larval nitrogen utilization efficiency increased as foliar N level decreased until N reached a level somewhere between 1.7%-1.2% below which it decreased. There appeared to be an N concentration threshold above which P. atomaria larvae received adequate N by regulating consumption and nitrogen utilization efficiency but below which they could no longer accumulate enough N by compensation to maintain an optimum growth rate and development time. Effects of food quality variables on relative growth and consumption rates are presented and discussed.


Long-Term Assessment of Baseline Blood Biochemistry Parameters in Rainbow Trout (Oncorhynchus mykiss) Maintained under Controlled Conditions.
Twelve biochemical parameters were measured in serum blood samples from rainbow trout (Oncorhynchus mykiss) maintained under controlled conditions. Forty-five samples were taken every 3 months (T1-T4) over the course of one year to define baseline values. The effect of fish total weight (TW) was also evaluated. Principal component analysis showed a clear separation between T4 and T1, and T2 and T3, indicating an increase in certain biochemical parameters with weight. Linear regression analysis showed how TW significantly explained 11-67% of the variability observed for nine parameters out of 12. Pearson's correlation matrix showed a significant positive correlation (p < 0.05) between TW and albumin, alkaline phosphatase, alanine-aminotransferase, creatinine, gamma-glutamyl transferase, magnesium, phosphorus and total protein. Furthermore, significant correlations (p < 0.05) between the majority of the biochemical parameters were found, indicating that growth can influence several parameters at the same time. The present study provides several useful baseline values for assessing the health of O. mykiss, indicating that fish weight is an important factor for interpreting the blood biochemical profile.


Effects of dopamine replacement therapy on lower extremity kinetics and kinematics during a rapid force production task in persons with Parkinson disease.
Postural instability appears to be a dopamine resistance motor deficit in persons with Parkinson disease (PD); however, little is known about the effects of dopamine replacement on the relative biomechanical contributions of individual lower extremity joints during postural control tasks. To gain insight, we examined persons with PD using both clinical and laboratory measures. For a clinical measure of motor severity we utilized the Unified Parkinson Disease Rating Scale motor subsection during both OFF and ON medication conditions. For the laboratory measure we utilized data gathered during a rapid lower extremity force production task. Kinematic and kinetic variables at the hip, knee, and ankle were gathered during a counter movement jump during both OFF and ON medication conditions. Sixteen persons with PD with a median Hoehn and Yahr severity of 2.5 completed the study. Medication resulted in significant improvements of angular displacement for the hip, knee, and ankle. Furthermore, significant improvements were revealed only at the hip for peak net moments and average angular velocity compared to the OFF medication condition. These results suggest that dopamine replacement medication result in decreased clinical motor disease severity and have a greater influence on kinetics and kinematics proximally. This proximally focused improvement may be due to active recruitment of muscle force and reductions in passive restraint during lower extremity rapid force production.


Stomatal Sensitivity to Vapor Pressure Deficit and the Loss of Hydraulic Conductivity Are Coordinated in Populus euphratica, a Desert Phreatophyte Species.
There are considerable variations in the percentage loss of hydraulic conductivity (PLC) at mid-day minimum water potential among and within species, but the underpinning mechanism(s) are poorly understood. This study tested the hypothesis that plants can regulate leaf specific hydraulic conductance (K l) via precise control over PLC under variable ΔΨ (water potential differential between soil and leaf) conditions to maintain the -m/b constant (-m: the sensitivity of stomatal conductance to VPD; b: reference stomatal conductance at 1.0 kPa VPD), where VPD is vapor pressure deficit. We used Populus euphratica, a phreatophyte species distributed in the desert of Northwestern China, to test the hypothesis. Field measurements of VPD, stomatal conductance (g s), g s responses to VPD, mid-day minimum leaf water potential (Ψ lmin), and branch hydraulic architecture were taken in late June at four sites along the downstream of Tarim River at the north edge of the Taklamakan desert. We have found that: 1) the -m/b ratio was almost constant (=0.6) across all the sites; 2) the average Ψ 50 (the xylem water potential with 50% loss of hydraulic conductivity) was -1.63 MPa, and mid-day PLC ranged from 62 to 83%; 3) there were tight correlations between Ψ 50 and wood density/leaf specific hydraulic conductivity (k l) and between specific hydraulic conductance sensitivity to water potential [d(k s)/dln(-Ψ)] and specific hydraulic conductivity (k s). A modified hydraulic model was applied to investigate the relationship between g s and VPD under variable ΔΨ and K l conditions. It was concluded that P. euphratica was able to control PLC in order to maintain a relatively constant -m/b under different site conditions. This study demonstrated that branchlet hydraulic architecture and stomatal response to VPD were well coordinated in order to maintain relatively water homeostasis of P. euphratica in the desert. Model simulations could explain the wide variations of PLC across and within woody species that are often observed in the field.


COVID-19 lockdown: a boon in boosting the air quality of major Indian Metropolitan Cities.
The COVID-19 lockdown has not only helped in combating the community transmission of SARS-CoV-2 but also improved air quality in a very emphatic manner in most of the countries. In India, the first phase of COVID-19 lockdown came into force on March 25, 2020, which was later continued in the next phases. The purpose of this study was to investigate the result of lockdown on air quality of major metropolitan cities-Delhi, Mumbai, Kolkata, Chennai, Bengaluru, Hyderabad, Jaipur, and Lucknow-from March 25 to May 3, 2020. For this study, the concentration of six criteria air pollutants (PM2.5, PM10, CO, NO2, SO2, and O3) and air quality index during the COVID-19 lockdown period was compared with the same period of the previous year 2019. The results indicate a substantial improvement in air quality with a drastic decrease in the concentration of PM2.5, PM10, CO, and NO2, while there is a moderate reduction in SO2 and O3 concentration. During the lockdown period, the maximum reduction in the concentration of PM2.5, PM10, CO, NO2, SO2, and O3 was observed to be - 49% (Lucknow), - 57% (Delhi), - 75% (Mumbai), - 68% (Kolkata), - 48% (Mumbai), and - 29% (Hyderabad), respectively. The value of the air quality index (AQI) also dwindled significantly during the COVID-19 lockdown period. The maximum decline in AQI was observed - 52% in Bengaluru and Lucknow. The order of AQI was satisfactory > moderate > good > poor and the frequency order of prominent pollutants was O3 > PM10 > PM2.5 > CO > NO2 > SO2 during the lockdown period in all the aforementioned metropolitan cities.


Evaluation of an improved small gauge needle for venipuncture in children with difficult venous access: Impact on sample quality, phlebotomist satisfaction and patient pain perception.
Smaller needles gauge (G) may reduce pain and improve vein access in difficult venous access (DVA). Aims were to compare the performances of two Beckton-Dickinson (BD) Vacutainer® Blood Collection Sets in a pediatric setting: UltraTouch™ Push Button (UT-PBBCS) and Safety-Lok™ (SLBCS). Questionnaires were used to record venipuncture features, patient pain perception and phlebotomist difficulty score. Specimen quality was evaluated by hemolysis index (HI) on Roche Cobas® 6000. SLBCS (21/23G) or UT-PBBCS (23/25G) were used in 211 (50.2%) and 209 (49.8%) subjects. Pain was associated with age (p < 0.0001) and was lower in UT-PBBCS (p = 0.0339). Difficulty was significantly associated with age (p = 0.002), not with needle gauge (p = 0.461) and it was 0.42 points lower in UT-PBBCS. HI was not associated with blood collection set (p = 0.385). UT-PBBCS globally performed better than SLBCS and could enhance phlebotomy and patient comfort, without affecting sample quality in pediatric patients with DVA.


Demonstration in living cells of an intragenic negative regulatory element within the rodent c-fos gene.
We studied c-fos gene expression in rat fibroblasts by microinjection of regulatory DNA sequences, such as the serum response element (SRE) present in c-fos promotor, in order to compete directly with such sequences for binding of putative regulatory factors. We show that an additional fos intragenic regulatory element (FIRE) is located at the end of exon 1. When coinjected with an SRE oligonucleotide, it induced c-fos expression in quiescent cells, whereas injection of SRE sequence alone failed to do so. Moreover, injection in quiescent cells of an SRE oligonucleotide together with a p-fos-lacZ construct containing the c-fos SRE as well as an in-frame insertion of FIRE resulted in a block to beta-galactosidase expression that can be relieved by coinjection of the FIRE sequence.


[What does it mean to see? (author's transl)].
A short discussion is given of the phylogenesis of visual organ and what the word: "to see" can mean. The author concludes that we still have a long way to understand fully the very complicated mechanism of the vision.


[An attempt to recover aesthetic appearance and mastication to a patient having strong vomiting reflex].
A 37 year-old male visited the hospital with aesthetic dissatisfaction and mastication functional disease due to multiple tooth loss as thr chief complaint. As the patient had a strong gagging reflex, intravenous sedation and inhalation sedation were used, enabling full-mouth prosthetic treatment to be performed. Improvement of aesthetic dissatisfaction and recovery of mastication function were considered to have been achieved with fixed prosthetic restoration alone, allowing the specific occlusal relationship to be maintained. The procedure was made possible by controlling the patient's dental phobia and gagging reflex with sedation and performing the restoration prosthesis treatment in each block while the patient was sedated. As the patient's gagging reflex exhibited reduced sensitivity following treatment, it was considered to have a significant psychogenic component: this must be taken into account in future treatment so that medical staff avoid instigating or exacerbating the patient's gagging reflex.


Immunocytochemical studies on light-induced changes in phosphatidylinositol 4,5-bisphosphate immunoreactivity in the visual system of normal and norpA mutant of Drosophila.
The distribution of phosphatidylinositol 4,5-bisphosphate (PIP2) in the visual system of Drosophila was studied by indirect immunofluorescence staining using a monoclonal antibody against PIP2. The retina of the compound eye and the cortical regions of the optic lobe were heavily stained by the antibody. In the retina, photoreceptor cells were stained with the antibody, but non-neuronal cells such as pigment cells and cone cells were not stained. The staining intensity in the light-adapted photoreceptor cells was lower than that in dark-adapted cells in normal flies, whereas no such difference in immunoreactivity was observed in the norpAEE5 mutant, whose photoreceptor cells are deficient in phospholipase C. These results suggest that the PIP2 in the photoreceptor cells is hydrolyzed by phospholipase C coded by the norpA gene upon light stimulation.


Microchromatography of hemoglobins. VIII. A general qualitative and quantitative method in plastic drinking straws and the quantitative analysis of Hb-F.
The microchromatographic procedure for the quantitative analysis of the hemoglobin components in a hemolysate uses columns of DEAE-cellulose in a plastic drinking straw with a glycine-KCN-NaCl developer. Not only may the method be used for the quantitative analysis of Hb-F but also for the analysis of the varied components in mixtures of hemoglobins.


Annular atrophic lichen planus induced by anti-HER2 antibodies.
Pertuzumab and trastuzumab are monoclonal antibody inhibitors targeting human epidermal growth factor receptor 2 (HER-2) and are increasingly being utilised in the management of HER2-positive breast cancer, having been demonstrated to improve progression-free survival in conjunction with docetaxel. We present a rare presentation of a lichenoid drug eruption, in an annular atrophic variant, in a 35-year-old woman after initiation of HER2-inhibitor (pertuzumab and trastuzumab) therapy for metastatic breast cancer.


Hysteroscopy safety.
Hysteroscopy is a very common tool providing the gynecologist the ability to diagnose and treat a variety of intrauterine disorders. This outpatient therapy has provided quick and effective relief for women worldwide. Although simple in concept, hysteroscopy is associated with minor and major complications. Awareness of these difficulties and methods of prevention and management is key to good surgical outcomes. This article reviews well tolerated practices for hysteroscopy complications. Although complications with both diagnostic and operative hysteroscopy are rare, they can often be prevented with thorough preoperative evaluation and appropriate intraoperative decision making. Understanding the patient, disorder, and surgical process can assist the surgeon in providing the best outcome for the patient. With appropriate training and education, gynecologists can safely incorporate hysteroscopy into their surgical practice.


Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces.
Circular tandem repeat proteins ('cTRPs') are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubility, a wide range of sizes, and are useful as protein display particles for biotechnology applications. However, cTRPs also demonstrate inefficient self-assembly from smaller subunits. In this study, we describe a new generation of cTRPs, with longer repeats and increased interaction surfaces, which enhanced the self-assembly of two significantly different sizes of homotrimeric constructs. Finally, we demonstrated functionalization of these constructs with (1) a hexameric array of peptide-binding SH2 domains, and (2) a trimeric array of anti-SARS CoV-2 VHH domains. The latter proved capable of sub-nanomolar binding affinities towards the viral receptor binding domain and potent viral neutralization function.


Characterizing spatiotemporal variations of chromophoric dissolved organic matter in headwater catchment of a key drinking water source in China.
Natural surface drinking water sources with the increasing chromophoric dissolved organic matter (CDOM) have profound influences on the aquatic environment and drinking water safety. Here, this study investigated the spatiotemporal variations of CDOM in Fengshuba Reservoir and its catchments in China. Twenty-four surface water samples, 45 water samples (including surface water, middle water, and bottom water), and 15 pore water samples were collected from rivers, reservoir, and sediment of the reservoir, respectively. Then, three fluorescent components, namely two humic-like components (C1 and C2) and a tryptophan-like component (C3), were identified from the excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC) for all samples. For spatial distributions, the levels of CDOM and two humic-like components in the reservoir were significantly lower than those in the upstream rivers (p < 0.01), indicating that the reservoir may act as a reactor to partly reduce the levels of exogenous input including CDOM and humic-like matters from the surrounding catchment. For temporal variations, the mean levels of CDOM and three fluorescent components did not significantly change in rivers, suggesting that perennial anthropic activity maybe an important factor impacting the concentration and composition of river CDOM but not the precipitation and runoff. However, these mean values of CDOM for the bulk waters of the reservoir changed markedly along with seasonal variations, indicating that the hydrological processes in the reservoir could control the quality and quantity of CDOM. The different correlations between the fluorescent components and primary water parameters in the river, reservoir, and pore water samples further suggest that the reservoir is an important factor regulating the migration and transformation of FDOM along with the variations of different environmental gradients.


Computer keyboarding biomechanics and acute changes in median nerve indicative of carpal tunnel syndrome.
Carpal tunnel syndrome is a common and costly peripheral neuropathy. Occupations requiring repetitive, forceful motions of the hand and wrist may play a role in the development of carpal tunnel syndrome. Computer keyboarding is one such task, and has been associated with upper-extremity musculoskeletal disorder development. The purpose of this study was to determine whether continuous keyboarding can cause acute changes in the median nerve and whether these changes correlate with wrist biomechanics during keyboarding. A convenience sample of 37 healthy individuals performed a 60-minute typing task. Ultrasound images were collected at baseline, after 30 and 60 min of typing, then after 30 min of rest. Kinematic data were collected during the typing task. Variables of interest were median nerve cross-sectional area, flattening ratio, and swelling ratio at the pisiform; subject characteristics (age, gender, BMI, wrist circumference, typing speed) and wrist joint angles. Cross-sectional area and swelling ratio increased after 30 and 60 min of typing, and then decreased to baseline after 30 min of rest. Peak ulnar deviation contributed to changes in cross-sectional area after 30 min of typing. Results from this study confirmed a typing task causes changes in the median nerve, and changes are influenced by level of ulnar deviation. Furthermore, changes in the median nerve are present until cessation of the activity. While it is unclear if these changes lead to long-term symptoms or nerve injury, their existence adds to the evidence of a possible link between carpal tunnel syndrome and keyboarding.


[The UHSA, an improvement in the care provision].
Established by the law on the orientation and programming of justice of September 2002, the specially equipped hospital unit (UHSA) provides psychiatric treatment with full medical care to prisoners, in direct cooperation with the prison. In this specific social context, can the organisation of the care and the structure itself represent a lasting solution?


Antitumor effects of human lymphoblastoid interferon on advanced renal cell carcinoma.
Human lymphoblastoid interferon alpha was administered intramuscularly at a dose of 3 times 10(6) units per day to 25 patients with advanced renal cell carcinoma. Six patients (24.0 per cent) showed objective responses, including 2 with complete regression of tumors. Nine patients (37.5 per cent) showed disease stabilization, while the disease progressed in 9 others (37.5 per cent). All tumor responses (2 complete, 4 partial and 2 mixed responses) were seen in lung, skin and liver metastases in patients whose primary tumors had been removed. Mean time to response was 87 +/- 74 days (range 28 to 240 days) and mean duration of response was 6.5 +/- 6.4 months (range 1 to greater than 20 months). Human lymphoblastoid interferon alpha was a potential active antitumor agent in patients with advanced renal cell carcinoma.


Fetal male gender and the benefits of treatment of mild gestational diabetes mellitus.
We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender. This is a secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes. Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass (P = .04) and birthweight percentile (P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes. The magnitude of the reduction of a newborn's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates.


Understanding and mimicking the dual optimality of the fly ear.
The fly Ormia ochracea has the remarkable ability, given an eardrum separation of only 520 μm, to pinpoint the 5 kHz chirp of its cricket host. Previous research showed that the two eardrums are mechanically coupled, which amplifies the directional cues. We have now performed a mechanics and optimization analysis which reveals that the right coupling strength is key: it results in simultaneously optimized directional sensitivity and directional cue linearity at 5 kHz. We next demonstrated that this dual optimality is replicable in a synthetic device and can be tailored for a desired frequency. Finally, we demonstrated a miniature sensor endowed with this dual-optimality at 8 kHz with unparalleled sound localization. This work provides a quantitative and mechanistic explanation for the fly's sound-localization ability from a new perspective, and it provides a framework for the development of fly-ear inspired sensors to overcoming a previously-insurmountable size constraint in engineered sound-localization systems.


KCNA2-Related Epileptic Encephalopathy.
Investigators from the University Leipzig and University of Tübingen report mutations of KCNA2 as a novel cause of epileptic encephalopathy.


Clinical significance of "periventricular collateral enhancement sign" in symptomatic moyamoya disease: A vessel wall imaging study.
Periventricular collaterals are associated with high risk of hemorrhagic stroke in adult moyamoya disease (MMD). However, the clinical significance of the periventricular collateral enhancement sign (PCES), which indicates wall enhancement of periventricular collaterals on contrast-enhanced vessel wall imaging (VWI), has yet to be determined. Thirty-seven patients with MMD with acute neurological symptoms were consecutively recruited. Periventricular collaterals including lenticulostriatal artery, thalamic artery, and choroidal artery collaterals were evaluated on digital subtraction angiography, and then PCES was detected on pre- and postcontrast VWI. First, the association between PCES and hemorrhagic presentation was evaluated using multivariate analyses. Second, two raters investigated the culprit vessels responsible for bleeding in hemorrhagic MMD using the Cohen kappa statistic. Fifteen sites of PCES on postcontrast VWI were observed in 15 patients. Multivariate analysis revealed that hemorrhagic presentation was the only independent factor for PCES (OR = 37.3, 95%CI = 3.9-113, p =.002). In patients with hemorrhagic presentation (n = 20), the identification rate of the ruptured vessel was 80% by rater 1, with excellent agreement. (inter-rater, κ = 0.86, 95%CI = 0.59-1.00; intra-rater, κ = 0.83, 95%CI = 0.50-1.00). Choroidal (50%) and thalamic artery collaterals (15%) were the most common and the second most common types of culprit vessels. Inter-rater and intra-rater reliabilities for the classification of culprit vessels were also excellent (intra-rater, κ = 0.86, 95%CI = 0.67-1.00; inter-rater, κ = 0.93, 95%CI = 0.79-1). Acute hemorrhagic stroke in MMD is independently associated with PCES on postcontrast VWI. PCES can help to detect the culprit vessels that are responsible for hemorrhage in patients with MMD.


RP1-59D14.5 triggers autophagy and represses tumorigenesis and progression of prostate cancer via activation of the Hippo signaling pathway.
Prostate cancer (PCa) is one of the major malignant tumors among men worldwide. Long noncoding RNAs (lncRNAs) have been documented as important modulators in human cancers, including PCa. In our study, we investigated the role and potential mechanism of RP1-59D14.5 in PCa. RP1-59D14.5 expressed at a low level in PCa cells. Gain-of-function assays including colony formation and transwell assays displayed that RP1-59D14.5 overexpression repressed PCa cell proliferation, migration, and invasion. Besides, RP1-59D14.5 up-regulation induced autophagy in PCa cells. Mechanically, luciferase reporter assays and western blot verified that RP1-59D14.5 activated the Hippo pathway in PCa cells. Through RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we validated that RP1-59D14.5 functioned as a competing endogenous RNA (ceRNA) to regulate large tumor suppressor kinase 1/2 (LATS1/2) via targeting miR-147a. Moreover, RP1-59D14.5 recruited HUR to promote casein kinase 1 (CK1) expression. Collectively, RP1-59D14.5 promoted yes-associated protein (YAP) degradation to activate the Hippo pathway in PCa progression via targeting the miR-147a/LATS1/2 axis and recruiting HUR to promote the interaction of CK1 and β-transducin repeat-containing protein (βTrCP). These results implied that RP1-59D14.5 acted as a tumor suppressor in PCa, which might be a target for PCa treatment.


Somatostatin: analogs with selected biological activities.
[D-Cys14]-Somatostatin is the first analog of somatostatin found to be more potent in inhibiting glucagon and growth hormone secretion that it is in inhibiting insulin secretion. [D-Trp8]-Somatostatin is eight to ten times more potent than somatostatin in inhibiting insulin, glucagon, and growth hormone secretion. [D-Trp8, D-Cys14]-Somatostatin is more potent than [D-Cys14]-Somatostatin, but retains its relative selectivity in being a more potent inhibitor of the secretion of glucagon and growth hormone than of insulin.


Sequence-specific chemical modification of a hybrid bacteriophage M13 single-stranded DNA by alkylating oligonucleotide derivatives.
Alkylating oligonucleotide derivatives react with the complementary sequences in hybrid M13mp7 bacteriophage single-stranded DNA and destroy the infecting ability of the DNA. The reagents do not damage M13mp9 single-stranded DNA lacking the target nucleotide sequence.


The role of attentional control over interference in minor hallucinations in Parkinson's disease.
Minor hallucinations in Parkinson's disease are associated with connectivity changes in attentional networks and increased risk of structured hallucinations. However, the clinical translation of these abnormalities in attention processes is not well-defined, and commonly used neuropsychological tests are not able to detect significant deficits in Parkinson's disease patients with isolated minor hallucinations. To analyze the behavioral and electrophysiological correlates of minor hallucinations in Parkinson's disease during an attentional task assessing response inhibition and interference control. Fifty-five non-demented Parkinson's disease patients with (PD-mH; n = 27) and without minor hallucinations (PD-NH; n = 28) were included in the analysis. An Ericksen flanker task was performed to compare the effect of presenting congruent and incongruent stimuli on accuracy, reaction times and stimulus-locked event-related potentials morphology. Although both groups showed equivalent performance in a standard neuropsychological assessment, in the flanker task accuracy rates were lower in the PD-mH group in incongruent trials (p = 0.005). In the event-related potentials, PD-mH patients showed increased amplitude of the N2 at Fz [t(53); p < 0.05] and decreased amplitude of the P300 at Pz [t(53); p < 0.05] for the incongruent trials. Parkinson's disease patients with isolated minor hallucinations were more susceptible to interference mediated by irrelevant stimuli and had less cognitive control for suppressing these interferences. The failure of these systems could precipitate the intrusion and overrepresentation of peripheral irrelevant stimuli perceived as minor hallucinations. The Ericksen flanker task could be used as a sensitive clinical marker of the attentional defects leading to hallucinations in Parkinson's disease.


Changes in blood biochemistry in mice during development of experimental depression.
Biochemical parameters of the plasma were studied in mice at different stages of the development of depression-like states in males after social defeats in 10 and 20 intermale confrontations (T10 and T20 victims, respectively). Glucose and cholesterol levels were increased in T10 victims in comparison with intact animals. In T20 victims the increase in glucose level was paralleled by an increase in total protein. T20 victims differed from T10 victims by lower catalase activity.


Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.
To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.


Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family.
Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-1 cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism.


Long-term prevention of catheter-associated urinary tract infections among critically ill patients through the implementation of an educational program and a daily checklist for maintenance of indwelling urinary catheters: A quasi-experimental study.
Removing an indwelling urinary catheter as soon as possible is the cornerstone of catheter-associated urinary tract infections (CAUTI) prevention. However, implementing this measure may be challenging in clinical settings. To evaluate the impact of implementing a healthcare workers (HCWs) educational program and a daily checklist for indwelling urinary catheter indications among critical patients on the incidence of CAUTI. This was a quasi-experimental study performed in a general intensive care unit of a tertiary-care hospital over a 12 years period, from January 1, 2005 to December 31, 2016. Rates of urinary catheter use and incidence density of CAUTI were monthly evaluated following the Centers for Disease Control and Prevention (CDC) criteria throughout the study period. Phase I (2005-2006) was the pre-intervention period. In phase II (2007-2010), HCWs routine training on CAUTI prevention was performed twice-a-year. In phase III (2011-2014), we implemented a daily checklist for indwelling urinary catheter indications, in addition to the biannual training. In phase IV, (2015-2016) the biannual training was replaced by training only newly hired HCWs and the daily checklist was maintained. The mean rate of urinary catheter utilization decreased from phase I to phase IV (73.1%, 74.1%, 54.9%, and 45.6%, respectively). Similarly, the incidence density of CAUTI decreased from phase I to phase IV (14.9, 7.3, 3.8, and 1.1 per 1000 catheter-days, respectively). HCWs education and daily evaluation of indwelling urinary catheter indications were highly effective in reducing the rates of catheter utilization as well as the incidence density of CAUTI.


Developing Angelman syndrome-specific clinician-reported and caregiver-reported measures to support holistic, patient-centered drug development.
Angelman syndrome (AS) is a rare, heterogenous neurogenetic condition, which significantly impacts the lives of people with AS and their families. Valid and reliable measures reporting key symptoms and functional impairments of AS are required to support development of patient-centered therapies. We describe the development of clinician- and caregiver-reported, AS-specific Global Impression scales for incorporation into clinical trials. Best practice US Food and Drug Administration guidance for measure development was followed with input from expert clinicians, patient advocates, and caregivers during content generation and refinement. Initial measurement domains for the Symptoms of AS-Clinician Global Impression (SAS-CGI) and the Caregiver-reported AS Scale (CASS) were identified from a conceptual disease model of AS symptoms and impacts, derived from interviews with caregivers and clinicians. Two rounds of cognitive debriefing (CD) interviews were performed; clinicians debriefed the SAS-CGI, with patient advocates and caregivers debriefing the CASS to ensure relevance and comprehension. Feedback was used to refine items and ensure wording was age-appropriate and captured AS-specific symptoms, as well as associated impacts and functional impairments. The SAS-CGI and CASS capture global assessments of seizures, sleep, maladaptive behaviors, expressive communication, fine and gross motor skills, cognition, and self-care, which were determined by clinicians, patient advocates, and caregivers to be the most challenging aspects of AS. Additionally, the measures include items for assessing overall AS symptoms and the meaningfulness of any change. In addition to ratings for severity, impact, and change, a notes field was included in the SAS-CGI to provide the rationale for the chosen rating. CD interviews confirmed the measures covered key concepts of AS from the perspective of clinicians and caregivers, and demonstrated that the measures' instructions, items, and response options were clear and appropriate. Interview feedback informed adjustments to the wording of the instructions and the items. The SAS-CGI and CASS were designed to capture multiple AS symptoms, reflecting the heterogeneity and complexity of AS in children 1 to 12 years old. These clinical outcome assessments have been incorporated into AS clinical studies, which will allow for the evaluation of their psychometric properties and inform further refinements if needed.


Bioactive compounds and health-promoting properties of berry fruits: a review.
This study characterizes biologically active compounds of berry fruits, including non-nutritive compounds such as phenolic compounds, including anthocyanins, phenolic acids, stilbens and tannins, as well as nutritive compounds such as carotenoids and vitamin C. It discusses the biological activity of those compounds, in particular their antioxidant properties and the resulting health benefits.


Nutritional and hormonal regulation of articular collagen production in diabetic animals.
Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P less than .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, beta-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that approximately 31 to 32% of the defect was due to undernutrition, leaving approximately 68-69% of the defect due to the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)


Measuring emergency department nurses' attitudes towards deliberate self-harm using the Self-Harm Antipathy Scale.
The emergency department is an important gateway for the treatment of self-harm patients. Nurses' attitudes towards patients who self-harm can be negative and often nurses experience frustration, helplessness, ambivalence and antipathy. Patients are often dissatisfied with the care provided, and meeting with positive or negative attitudes greatly influences whether they seek additional help. A quantitative design was utilised to measure emergency department nurses' attitudes towards deliberate self-harm. The 'Self-Harm Antipathy Scale', a validated questionnaire, was administered to a random sample of nurses in four emergency departments in the Republic of Ireland. A total of 87 questionnaires were returned (87% response rate). Results reveal that nurses show slightly negative antipathy overall, indicating positive attitudes towards self-harming patients. Attitudes were significantly different in accordance with a nurse's age. Education and social judgment also contribute to the way nurses view, interact and make moral decisions regarding self-harm patients. Evidence indicates there is need to improve the training, supervision and support of nurses caring for patients who self-harm, and that practical strategies should be implemented to manage the alienation process and inform practice.


Spatial analysis and modelling for primary healthcare site selection in Midnapore town, West Bengal.
Unprecedented and chaotic growth of cities results in reducing open spaces and water bodies, worsening infrastructure facilities and changes in ecological morphology. This unregulated growth of the urban population led to uneven distribution of urban amenities, facilities and healthcare services. Considering this, the study aimed to draw attention to the existing spatial pattern of healthcare facility centres as well as to find out the possible sites for the provision of healthcare facility centres in the municipal ward (micro-scale) of Midnapore town. This prototype study was conducted using Analytical Hierarchy Process (AHP) and Ordinary Least Square (OLS) evaluation model based on various criteria through Arc GIS environment. The findings indicate that the spatial distribution patterns of existing public healthcare centres were significantly dispersed. Weights based on a set of criteria were calculated by AHP and OLS algorithm and generated suitability evaluation maps classified from 1 (poor suitable) to 4 (most suitable). According to the employed criteria in this study unveil those existing hospitals and primary healthcare centres have not been located in the appropriate locations. The model is found to be valid for the given study area and there is no significant difference between AHP and OLS results. Further, it can be used for preparing the suitability map for the other areas with similar geo-environmental conditions for the proviso of healthcare services as well as will be most effective in preventing disease progression and reducing healthcare inequality on a large scale. The online version contains supplementary material available at 10.1007/s10708-021-10528-w.


Differential susceptibilities of Holtzman and Sprague-Dawley rats to fetal death and placental dysfunction induced by 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD) despite the identical primary structure of the aryl hydrocarbon receptor.
A single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioin (TCDD) administered to pregnant Holtzman (HLZ) rats on gestational days 15 (GD15) caused placental dysfunction, resulting in fetal death (Ishimura, R., Ohsako, S., Miyabara, Y., Sakaue, M., Kawakami, T., Aoki, Y., Yonemoto, J., Tohyama, C., 2002a. Increased glycogen content and glucose transporter 3 mRNA level in the placenta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 178, 161-171; Ishimura, R., Ohsako, S., Kawakami, T., Sakaue, M., Aoki, Y., Tohyama, C., 2002b. Altered protein profile and possible hypoxia in the placenta of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed rats. Toxicol. Appl. Pharmacol. 185, 197-206). In order to investigate the mechanism underlying the TCDD-induced fetal death, we compared two outbred strains of rats, namely, the HLZ and the Sprague-Dawley International Genetic Standard rats (SD-IGS), a strain with characteristics resembling those of the HLZ rats. Pregnant HLZ and SD-IGS rats were administered TCDD as a single dose by gavage on GD15, as described within the parentheses (HLZ, 0, 1.6 mug TCDD/kg; SD-IGS, 0, 2, 5, 10 microg TCDD/kg). Whereas a high incidence (14%) of fetal death was observed on GD20 in the HLZ rats, no fetal deaths occurred in the SD-IGS rats, even at the highest dose of TCDD. A histological marker of cellular abnormality at the placental junctional zone, i.e., delay in the disappearance of the glycogen cells and cysts filled with an eosinophilic material (GC-EM), which normally disappear by GD20, was observed in the HLZ rats after exposure to the lowest dose of TCDD (1.6 microg TCDD/kg), but not in the SD-IGS rats even after exposure to the highest dose of TCDD. Furthermore, maternal blood sinusoids in the labyrinth zone were constricted following exposure to TCDD in the HLZ, but not SD-IGS rats. These observations indicate that HLZ rats are more susceptible to the adverse effects of TCDD on fetal growth and placental function, than SD-IGS rats. Direct sequencing analysis of the aryl hydrocarbon receptor (AhR) gene revealed no difference in the primary structure of the receptor between the HLZ and SD-IGS rats. In addition, no significant differences were observed between the two strains of rats in the levels of induction of placental cytochrome P450 1A1, 1B1, AhR, and AhRR mRNAs following administration of serially increasing doses of TCDD (0.0125, 0.05, 0.2, 0.8, and 1.6 microg TCDD/kg), indicating that the activity of TCDD-AhR complex in the placenta is similar between the HLZ and SD-IGS rats. Taken together, the above-described findings indicate that the higher susceptibility of HLZ rats to TCDD-induced placental dysfunction and fetal death may be modulated by other factor(s) in the genetic background of HLZ rats than the AhR.


Human Milk Fortification for Very Preterm Infants: Toward Optimal Nutrient Delivery, Neonatal Intensive Care Unit Growth, and Long-Term Outcomes.
Human milk is the preferred diet for very preterm infants due to short-term and long-term benefits for health and neurodevelopment. Fortification of human milk is required to deliver sufficient nutrients to attain recommended growth targets during the neonatal hospitalization. Intrinsic variability in human milk composition poses a challenge in clinical practice because some infants fail to meet recommended nutrient intakes even with existing approaches of standard (fixed-dose) and adjustable fortification. Individually targeted fortification is an emerging strategy to minimize nutrition delivery gaps through application of point-of-care human milk analysis and has potential to improve growth and related outcomes.


Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression.
The Hox-1.6 gene disrupted in embryonic stem cells by homologous recombination was introduced into the mouse germline. Heterozygous mice were normal, but homozygous mice died at birth from anoxia and had numerous defects that were centered at the level of rhombomeres 4 to 7 and included delayed hindbrain neural tube closure, absence of certain cranial nerves and ganglia, and malformed inner ears and bones of the skull. Thus, Hox-1.6 is involved in regional specification along the rostrocaudal axis, but only in its most rostral domain of expression. Hox-1.6 appears to specify neurogenic neural crest cells prior to specification of mesenchymal neural crest cells by Hox-1.5. Thus, within the same region of the presumptive hindbrain, two HOX-1 genes are involved in the patterning of two different populations of neural crest cells. The implication of these results for the function of the Hox network during mouse embryogenesis is discussed.


Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody.
Protamine is used widely to reverse the anticoagulant effects of heparin and to delay the absorption of insulin. Although adverse reactions to protamine are reported infrequently and are usually mild, we recently observed the first fatal case of type I anaphylaxis resulting from protamine. This patient had previously been sensitized to protamine during cardiac catheterization and had high levels of protamine-specific immunoglobulin E in the serum. In a prospective study, we found that 10 of 19 diabetic patients (53%) who had received insulin containing insulin also had high levels of antiprotamine immunoglobulin E. In contrast, none of 27 nondiabetic healthy normal controls or 10 diabetics who had never received protamine or protamine-containing insulin had levels of antiprotamine immunoglobulin E over background. This study underscores the risks of routinely administering protamine to susceptible individuals and the need for alternative therapies.


Molecular epidemiology of Haemophilus influenzae type b isolated from children with clinical cases of conjugate vaccine failures.
We analyzed eight invasive Haemophilus influenzae strains isolated from individual children vaccinated appropriately for their ages. Five of the strains were type b and three were nontypeable strains. Children infected with nontypeable strains had a protective level of anti-H. influenzae type b antibodies, while only one of the children whose cases represented true vaccine failure did.


Quantifying the Acute Care Costs of Neonatal Bacterial Sepsis and Meningitis in Mozambique and South Africa.
Sepsis and meningitis are among the leading causes of neonatal deaths in sub-Saharan Africa (SSA). Neonatal sepsis caused ~400 000 deaths globally in 2015, half occurring in Africa. Despite this, there are few published data on the acute costs of neonatal sepsis or meningitis, with none in SSA. We enrolled neonates admitted to 2 hospitals in South Africa and Mozambique between 16 April 2020 and 1 April 2021. In South Africa all cases were microbiologically confirmed, but in Mozambique both clinically suspected and microbiologically confirmed cases were included. Data were collected on healthcare resource use and length of stay, along with information on household expenditure and caregiving. We used unit costs of healthcare resources in local currencies to estimate healthcare provider costs per patient and costs per household. Results were converted to 2019 international dollars (I$). We enrolled 11 neonates in Mozambique and 18 neonates in South Africa. Mean length of stay was 10 days (median, 9 [interquartile range {IQR}, 4-14) and 16 days (median, 15 [IQR, 13-18]), respectively. In Mozambique we estimated mean household costs of I$49.62 (median, 10.19 [IQR, 5.10-95.12]) and hospitalization costs of I$307.58 (median, 275.12 [IQR, 149.43-386.12]). In South Africa these costs were I$52.31 (median, 30.82 [IQR, 19.25-73.08]) and I$684.06 (median, 653.62 [IQR, 543.33-827.53]), respectively. We found substantial costs associated with acute neonatal bacterial (all-cause) sepsis and meningitis in SSA. Our estimates will inform economic evaluations of interventions to prevent neonatal invasive bacterial infections.


New theoretical and experimental approaches on maternal motivation in mammals.
Maternal behavior is expressed in different modalities, physiological conditions, and contexts. It is the result of a highly motivated brain, that allows the female to flexibily adapt her caring activities to different situations and social demands. To understand how mothers coordinate maternal and other motivated behaviors we discuss the limitations of current theoretical approaches to study maternal motivation (e.g. distinction between appetitive and consummatory behaviors), and propose a different approach (i.e. motorically active vs. passive motivations) and a distinction between maternal motivated state and maternal motivated behaviors. We review the evidence supporting dopamine mediation of maternal motivation and describe how different phases of the dopaminergic response - basal, tonic, and phasic release in the nucleus accumbens - relate to increased salience, invigorating behavior, and behavioral switching. The existing and new experimental paradigms to investigate maternal motivation, and its coexpression and coordination with other social or non-social motivations are also analyzed. An example of how specificity of motivational systems (e.g. maternal and sexual behavior at postpartum estrus) could be processed at the neural level is also provided. This revision offers new theoretical and experimental approaches to address the fundamental question of how mothers flexibly adapt and coordinate the different components of maternal behavior with other motivated behaviors, also critical for the survival of the species.


Myofibrillar myopathies.
Myofibrillar myopathies (MFMs) are rare, inherited or sporadic, progressive neuromuscular disorders with considerable clinical and genetic heterogeneity. MFMs are defined morphologically by foci of myofibril dissolution that begins at the Z-disk, accumulation of myofibrillar degradation products, and ectopic expression of a large number of proteins including desmin. To date, mutations in six genes are known to cause MFMs, accounting for approximately half of the MFM patients identified. The causative genes encode mainly sarcomeric Z-disk(-related) proteins: desmin, αB-crystallin, myotilin, Z-band alternatively spliced PDZ motif containing protein (ZASP), filamin C and the antiapoptotic BCL2-associated athanogene 3 (Bag3). Although in most MFM patients the disease presents in adulthood and evolves slowly, some patients with desminopathy, αB-crystallinopathy or Bag3opathies have an infantile or juvenile disease onset. Cardiac involvement is very common in desminopathies and can sometimes be the initial or only symptom of the disease. Respiratory symptoms are noted during childhood in αB-crystallinopathies. Early severe cardiac and respiratory involvement is seen in Bag3opathies. Optical microscopic and immunohistochemical features are similar in MFMs; however, ultrastructural findings can be useful to differentiate between the distinct MFM subtypes. No curative treatment for MFMs is currently available. Careful follow-up, especially of cardiac and respiratory function, is important.


Dicyclo-hex-yl[4-(dimethyl-amino)-phen-yl]phosphine selenide.
In the title mol-ecule, C(20)H(32)NPSe, the P atom has a distorted tetra-hedral environment resulting in an effective cone angle of 172°. Weak inter-molecular C-H⋯Se inter-actions are observed.


Better survivals in adolescent and Young adults, compared to adults with acute lymphoblastic leukemia - A multicenter prospective registry in Thai population.
Adult acute lymphoblastic leukemia (ALL) is an uncommon hematologic malignancy with high relapse and mortality rate. This study aimed to describe characteristics and outcomes of Thai ALL patients, and to determine the differences between adolescent and young adult (AYA) and adult ALL. ALL patients aged > 15 years were prospectively enrolled from 2015 to 2017. AYA patients were defined as age ≤ 39 years. Out of the 188 enrolled ALL patients, 9 were excluded due to changes in diagnosis or incomplete data. From the remaining 179 patients, 103 (57.5%) were AYA and 76 (42.5%) were adult. AYA ALL patients were predominantly male, had higher T-cell phenotype, higher white blood cells and hemoglobin, with lower frequency of Philadelphia chromosome or BCR-ABL1 mutation. All patients received treatment by adult hematologist, however 40.8% of AYA ALL patients were treated with pediatric adapted protocol. The effects of stem cell transplantation (SCT) and age were determined by stratified patients as: AYA - no SCT 91 (51.1%), AYA - SCT 12 (6.7%), adult - no SCT 64 (36.0%) and adult - SCT 11 (6.2%). The 2-year overall survival were: 53.9%, 60.6%, 39.2% and 70.1%, respectively. The 2-year event-free survival were: 45.0%, 54.0%, 21.0% and 49.9%, respectively. This is a large multicenter ALL cohort study conducted in Thailand. Patients who underwent SCT showed significantly improved OS and EFS, confirming the benefit of graft-versus-leukemia effect in ALL. However, further studies with longer follow-up, expanded use of SCT, use of molecular data, and minimal residual disease status are warranted.


Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type.
Memory impairment is a process associated with alterations in neuronal plasticity, synapses formation, and stabilization. As the neural cell adhesion molecule (NCAM) plays a key role in synaptic bond stabilization, we analyzed the usefulness of soluble NCAM isoforms in the diagnosis of patients with dementia of the Alzheimer type (DAT). NCAM was measured in the sera of 70 control subjects and 43 DAT patients (with different severity of cognitive impairment, GDS), employing Western blot and densitometric quantification. LMW-NCAM bands (100-130 kDa) decreased significantly with age independently of sex. DAT patients presented values of LMW-NCAM and HMW-NCAM significantly higher than healthy controls of similar age (higher than 130 kDa). Only LMW-NCAM was associated with GDS. Our results suggest that NCAM could be involved in the pathogenesis of DAT disorder and that serum NCAM levels could be useful as differential diagnostic markers of the disease.


Spatial reference- (not working- or procedural-) memory performance of aged rats in the water maze predicts the magnitude of sulpiride-induced facilitation of acetylcholine release by striatal slices.
Cluster analysis of water-maze reference-memory performance distinguished subpopulations of young adult (3-5 months), aged (25-27 months) unimpaired (AU) and aged impaired (AI) rats. Working-memory performances of AU and AI rats were close to normal (though young and aged rats differed in exploration strategies). All aged rats showed impaired procedural-memory. Electrically evoked release of tritium was assessed in striatal slices (preloaded with [(3)H]choline) in the presence of oxotremorine, physostigmine, atropine+physostigmine, quinpirole, nomifensine or sulpiride. Aged rats exhibited reduced accumulation of [(3)H]choline (-30%) and weaker transmitter release. Drug effects (highest concentration) were reductions of release by 44% (oxotremorine), 72% (physostigmine), 84% (quinpirole) and 65% (nomifensine) regardless of age. Sulpiride and atropine+physostigmine facilitated the release more efficiently in young rats versus aged rats. The sulpiride-induced facilitation was weaker in AI rats versus AU rats; it significantly correlated with reference-memory performance. The results confirm age-related alterations of cholinergic and dopaminergic striatal functions, and point to the possibility that alterations in the D(2)-mediated dopaminergic regulation of these functions contribute to age-related reference-memory deficits.


Venous occlusions of the cavernous area--a complication of crushing fractures of the sphenoid bone.
Four patients who sustained crushing fractures of the sphenoidal bone had angiographic evidence of venous occlusions of the cavernous area. Signs depended upon the type of basal venous and cavernous anatomy. The diagnosis can be made by demonstrating abrupt cutoff of veins in the cavernous region, preferred retrograde flow of the anterior cavernous sinus, direct venous hemorrhage, and venous stasis.


Exercise Increases Pain Self-efficacy in Adults With Nonspecific Chronic Low Back Pain: A Systematic Review and Meta-analysis.
OBJECTIVE: To determine the effect of exercise on pain self-efficacy in adults with nonspecific chronic low back pain (NSCLBP). DESIGN: Intervention systematic review with meta-analysis LITERATURE SEARCH: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, PsycINFO, and CINAHL databases from October 20, 2018, to March 23, 2022. SELECTION CRITERIA: We included randomized controlled trials that compared the effect of exercise on pain self-efficacy to control, in adults with NSCLBP. DATA SYNTHESIS: We conducted a meta-analysis using a random-effects model. We evaluated the risk of bias using the Cochrane risk-of-bias tool (RoB 2) and judged the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. RESULTS: Seventeen trials were included, of which eight (n = 1121 participants; 60.6% female; mean age: 49.6 years) were included in the meta-analysis. Exercise increased pain self-efficacy by 3.02 points (95% confidence interval: 1.72, 4.32) on the 60-point Pain Self-Efficacy Questionnaire. The certainty of evidence was moderate; all trials were at high risk of bias. CONCLUSION: There was moderate-certainty evidence that exercise increased pain self-efficacy in adults with NSCLBP. Future research should investigate if this effect is meaningful, whether it increases with more targeted treatments to enhance pain self-efficacy, and the effects on outcomes for adults with NSCLBP. J Orthop Sports Phys Ther 2023;53(6):1-8. Epub: 10 May 2023. doi:10.2519/jospt.2023.11622.


Attribute capture underlying the precedence effect in rats.
In a reverberant environment, humans with normal hearing can perceptually fuse the soundwave from a source with its reflections off nearby surfaces into a single auditory image, whose location appears to be around the source. This phenomenon is called the precedence effect, which is based on the perceptual capture of the reflected (lagging) sounds' attributes by the direct wave from the source. Using the paradigm of attentional modulation of the prepulse inhibition (PPI) of the startle reflex, with both the prepulse-feature specificity and the perceived-prepulse-location specificity, this study was to examine whether the perceptual attribute capture underlying the precedence effect occurs in rats. One broadband continuous noise was delivered by each of two spatially separated left and right loudspeakers with a 1-ms inter-loudspeaker delay. A silent gap was embedded in one of the two noises as the prepulse stimulus. The results showed that regardless of whether the gap was physically in the leading or lagging noise when the leading noise was either the left or right one, fear conditioning the gap enhanced PPI only when the leading noise was delivered from the loudspeaker that was the leading but not the lagging loudspeaker during the conditioning, indicating that due to the spatial specificity (either left or right) in the attentional enhancement of PPI, the perceived location of the conditioned gap was always on the leading side even though the gap was physically on the lagging side. Thus, rats have the same perceptual ability of attribute capture, thereby experiencing the auditory precedence effect as humans.


Peritoneal lavage in the diagnosis of acute peritonitis.
The study was aimed at determining the value of peritoneal lavage as an aid in the diagnosis of acute peritonitis when the diagnosis could not be made by ordinary clinical criteria. Thirty patients were studied prospectively. Twenty-five of the patients were suspected of having peritonitis but doubt existed because of an unreliable history or equivocal or confusing abdominal signs. Five remaining patients were comatose and an intraabdominal source of sepsis needed to be excluded. The technique of lavage and criteria for diagnosis have been presented herein. There were 10 true-positive results, no false-positive results, 19 true-negative results, and one false-negative result (positive predictive value 100 percent, confidence level 95 percent). There were no complications due to the test. Peritoneal lavage is a useful method of diagnosing or excluding peritonitis in patients with confusing abdominal signs. Negative results of laparotomy or prolonged observation may thus be obviated in such patients.


Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency.
Pyruvate carboxylase deficiency is a rare metabolic disorder, with three different phenotypes. We aim to report the case of a newborn presenting the severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia and rigidity being the main features) and the results of the study of classic neurotransmitters involved in movement control. Hyperdopaminergic transmission (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic transmission (in the substantia nigra) were found. Both gamma-aminobutyric acid and dopamine markers were found coexisting in individual neurons of the substantia nigra. This is the first time this phenomenon has been reported in the literature. We discuss the possible role of GABAergic deficiency, its interaction with other neurotransmitters and its implication in neurotransmitter homeostasis. A better comprehension of that field would increase understanding of the pathophysiology of neurological symptoms and neurotransmitter plasticity.


Early repolarization pattern on ECG recorded before the acute coronary event does not predict ventricular fibrillation during ST-elevation myocardial infarction.
Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia. The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI. For STEMI patients admitted for primary percutaneous coronary intervention from 2007-2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression. ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER- groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER- patients (8.8%; P = .398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47-1.29; P = .324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23-1.001; P = .051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55-3.01; P = .569). In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI.


Reducing impaired driving through the identification of Repeat Target Vehicles: A case study.
One of the most persistent groups of impaired drivers that are seemingly unaffected by social pressure, moral appeals, and the fear of arrest is that of the repeat impaired driver. This smaller group accounts for a disproportionate number of all impaired driving trips, often with high blood alcohol contents. New approaches are needed to identify and deal with the repeat impaired driver. We propose a method based on the discovery that almost 10% of all impaired driving calls for service involve repeat vehicles. Using the number of times a vehicle appears in our data, the average time to repeat, and the personality characteristics of the repeat impaired driver, we are able to create a comprehensive and predictive description of a Repeat Target Vehicle (RTV). Our method provides an opportunity to explore new and innovative crime reduction strategies that were never before possible.


Improving imagery rescripting treatments: Comparing an active versus passive approach.
In imagery rescripting (ImRs), aversive mental images are modified to reduce symptoms in a variety of psychological disorders. However, uniform guidelines on how to optimally implement ImRs do currently not exist. It remains unclear whether therapists should stimulate patients to imagine themselves to actively intervene within the new image, or whether they may imagine helpers to change the situation. We aimed to compare these two variants of ImRs within an analogue experimental setting. After having watched an aversive film, one-hundred participants were randomly assigned to active ImRs (ImRs-A), passive ImRs (ImRs-P), imagery rehearsal (IRE), or no-intervention control (NIC). Participants were either instructed to rescript the film by imagining themselves intervening in the new script (ImRs-A) or encouraged to imagine helpers to intervene in the imagined situation (ImRs-P). Both ImRs increased mastery and elicited less distress than IRE with ImRs-P being experienced as less distressing than ImRs-A. Only ImRs-A led to a stronger increase in positive affect than IRE, whereas groups did not differ with respect to negative affect and self-efficacy. Conditions did not differ regarding the number of film-related intrusive memories. As a convenience sample was investigated, results cannot be generalized to clinical samples. Even though differences regarding symptomatic outcome could not be detected, ImRs-P was experienced as less distressing than ImRs-A. Results suggest that both ImRs lead to different processes during the intervention than mere exposure. Compared to IRE, ImRs increases mastery with ImRs-A and ImRs-P being equally effective.


Association of antibiotics and heavy metal arsenic to horizontal gene transfer from multidrug-resistant clinical strains to antibiotic-sensitive environmental strains.
The emergence of multidrug-resistant bacteria is currently posing a significant threat to global public health. By testing for resistance to different antibiotic classes, we discovered that the majority of clinical bacteria are multidrug-resistant. These clinical multidrug-resistant species have antibiotic resistance genes on their plasmids that can be horizontally transferred to various antibiotic susceptible environmental bacterial species, resulting in antibiotic-resistant transconjugates. Furthermore, we discovered that the presence of an optimal concentration of antibiotics or heavy metal (arsenic) facilitates horizontal gene transfer through the formation of transconjugants. Notably, the addition of a conjugation inhibitor (2-hexadecynoic acid, a synthetic fatty acid) completely blocked the formation of antibiotic or arsenic-induced transconjugants. We discovered a high level of arsenic in water from the Shukratal region, Uttarakhand, India, which corresponded to a high serum level of arsenic in clinically infected individuals from the Shukratal region compared to other locations in Uttarakhand. Importantly, bacterial strains isolated from infected people who drink water from the Shukratal region with high arsenic levels were found to be more antibiotic-resistant than strains isolated from other sites. We discovered that bacterial strains isolated from individuals with high serum arsenic levels are significantly more resistant to antibiotics than individuals with low serum arsenic levels within the Shurkratal. This research sheds light on imminent threats to global health in which improper clinical, industrial, and other waste disposal, increased antibiotic concentrations in the environment, and increased human interference can easily transform commensal and pathogenic bacteria found in environmental niches into life-threatening multidrug-resistant superbugs.


Effect of human follicle-stimulating hormone on immunomodulatory function of decidual mesenchymal stem cells by reducing interleukin-6 levels.
Women with an elevated basal FSH indicate diminished ovarian reserve and reduced oocyte and embryo numbers. DMSCs are likely to be involved in immune tolerance of pregnancy maintenance. We investigate the effect of follicle-stimulating hormones on the immunomodulatory functions of DMSCs. DMSCs were primary cultured from decidual tissue. Pretreated DMSCs with mitomycin C, combined with CD4+ T lymphocytes, DMSCs + CD4+T co-culture system was established. Different physiological dose FSH (3 ng/ml,10 ng/ml,30 ng/ml,100 ng/ml) were used to co-culture system. Cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, TNF-α) and other proteins (FSHR, MyD88) were measured. Compared with the control group (FSH (0 ng/mL) + CD4+T + DMSCs), the FSH concentration was 10, 30, and 100 ng/ml, IL-6 levels were significantly reduced (P < 0.05). IL-6, MyD88 protein expression was remarkably decreased (P < 0.05). FSH/FSHR could negatively regulate the immunosuppressive function of DMSCs by reducing secretion of IL-6 levels through MyD88 pathways, but upstream and downstream signalling pathways require further validation.


Artificial Nerve Containing Stem Cells, Vascularity and Scaffold; Review of Our Studies.
To promote nerve regeneration within a conduit (tubulation), we have performed studies using a tube model based on four important concepts for tissue engineering: vascularity, growth factors, cells, and scaffolds. A nerve conduit containing a blood vascular pedicle (vessel-containing tube) accelerated axon regeneration and increased the axon regeneration distance; however, it did not increase the number or diameter of the axons that regenerated within the tube. A vessel-containing tube with bone-marrow-derived mesenchymal stem cell (BMSC) transplantation led to the increase in the number and diameter of regenerated axons. Intratubularly transplanted decellularized allogenic nerve basal lamellae (DABLs) worked as a frame to maintain the fibrin matrix structure containing neurochemical factors and to anchor the transplanted stem cells within the tube. For the clinical application of nerve conduits, they should exhibit capillary permeability, biodegradability, and flexibility. Nerbridge® (Toyobo Co. Ltd., Osaka, Japan) is a commercially available artificial nerve conduit. The outer cylinder is a polyglycolic acid (PGA) fiber mesh and possesses capillary permeability. We used the outer cylinder of Nerbridge as a nerve conduit. A 20-mm sciatic nerve deficit was bridged by the PGA mesh tube containing DABLs and BMSCs, and the resulting nerve regeneration was compared with that obtained through a 20-mm autologous nerve graft. A neve-regeneration rate of about 70%-80% was obtained in 20-mm-long autologous nerve autografts using the new conduits.


Long-term treatment of dentine with triple antibiotic paste promotes stem cell viability and attachment.
Successful regenerative endodontic procedures in dental treatment are critically associated with complete disinfection of the root canal and require irrigants and medicaments. One factor for consideration is the biocompatibility of the medicament as this can affect the intracanal dentine and subsequently the dental stem cell viability required for the repair of the dentine-pulp complex. This in vitro study investigated the effect of a 4-week treatment of calcium hydroxide [Ca(OH)2] and triple antibiotic paste (TAP) on the irrigated radicular dentine by analysing dentine interaction with dental stem cells. TAP consists of metronidazole, ciprofloxacin and minocycline. Dentine chips were prepared and treated with either Ca(OH)2 or TAP for 4-weeks, irrigated by 1.5% sodium hypochlorite (NaOCl), rinsed with saline, followed by 17% ethylenediaminetetraacetic acid (EDTA). Dental pulp stem cells (DPSCs) cultured on the surface of the dentine chips were analysed on days 1, 3 and 7 of cell seeding for PrestoBlue viability assays, 6-diamidino-2 phenylindole (DAPI) staining and scanning electron microscopy (SEM). An independent t-test (SPSS software version 24.0) was used to statistically analyse the PrestoBlue assay data. DPSCs grown from dentine treated with TAP showed significantly higher cell viability than the Ca(OH)2 and control groups (p < 0.05). DAPI staining of the seeded DPSCs on the treated dental chips complemented the findings of the viability assay. SEM studies also revealed improvements in the cell spreading and attachment of DPSCs grown on TAP-treated dentine compared with Ca(OH)2. The treatment of dentine with TAP for 4 weeks provided a better microenvironment for the viability and attachment of DPSCs when compared to Ca(OH)2.


A simple biofilm model of bacterial competition for attached surface.
A simple biofilm model of competition in bacterial growth for an attached surface is developed. Competition for the attached surface is expressed with the crowded and detachment effects. The developed model is verified by comparing simulated results with data obtained in the experiments of batch culture of nitrifier and continuous treatment of actual sewage with biofilm reactor. This model can favorably simulate the growth competition between autotrophic and heterotrophic bacteria for the attached surface. Then some parameters for nitrification process are discussed with this model. It is clarified that the effective removal of organic matter before nitrification tank is required for effective nitrification in the biofilm reactor.


AOCT-NET: a convolutional network automated classification of multiclass retinal diseases using spectral-domain optical coherence tomography images.
Since introducing optical coherence tomography (OCT) technology for 2D eye imaging, it has become one of the most important and widely used imaging modalities for the noninvasive assessment of retinal eye diseases. Age-related macular degeneration (AMD) and diabetic macular edema eye disease are the leading causes of blindness being diagnosed using OCT. Recently, by developing machine learning and deep learning techniques, the classification of eye retina diseases using OCT images has become quite a challenge. In this paper, a novel automated convolutional neural network (CNN) architecture for a multiclass classification system based on spectral-domain optical coherence tomography (SD-OCT) has been proposed. The system used to classify five types of retinal diseases (age-related macular degeneration (AMD), choroidal neovascularization (CNV), diabetic macular edema (DME), and drusen) in addition to normal cases. The proposed CNN architecture with a softmax classifier overall correctly identified 100% of cases with AMD, 98.86% of cases with CNV, 99.17% cases with DME, 98.97% cases with drusen, and 99.15% cases of normal with an overall accuracy of 95.30%. This architecture is a potentially impactful tool for the diagnosis of retinal diseases using SD-OCT images.


Role of endoplasmic reticulum stress in hepatic glucose and lipid metabolism and therapeutic strategies for metabolic liver disease.
The endoplasmic reticulum is the most abundant membrane organelle in eukaryotic cells. It is an important site of membrane and secretory protein folding and glycolipid synthesis and transport, and it is responsible for regulating intracellular calcium homeostasis. When the load of protein synthesis and folding exceeds the processing capacity of the endoplasmic reticulum, the excessive accumulation of misfolded proteins leads to endoplasmic reticulum stress and activates the cellular unfolded protein response. Hepatocytes contain an abundance of smooth and rough endoplasmic reticulum, which can sense changes in various nutritional metabolic and external stimuli and mediate the regulation of glucose and lipid metabolism by activating the unfolded protein response signaling pathways. Endoplasmic reticulum stress plays a very important role in metabolic regulation and in the occurrence and development of liver diseases. This review summarizes the recent research progress on the unfolded protein response and hepatic glucose and lipid metabolism and discusses the mechanism linking endoplasmic reticulum stress with glucose and lipid metabolism disorders and related metabolic liver diseases to improve the understanding of the molecular pathological basis of major chronic diseases such as obesity, type II diabetes and nonalcoholic fatty liver disease.


One-pot synthesis of 4-arylidene imidazolin-5-ones by reaction of amino acid esters with isocyanates and α-bromoketones.
A simple and new multicomponent reaction for the one-pot synthesis of substituted 4-arylidene imidazolin-5-ones from l-amino acid methyl esters, iso-, isothio- or isoselenocyanates, and α-bromoketones is demonstrated. Isolation of thiohydantoin and 5-benzylidene 2-thioxoimidazolidin-4-one intermediates revealed a possible reaction mechanism. The strategy was further extended to the synthesis of 2-iminothiazolines and 2-thioxoimidazolin-4-ones.


Limulus ventral photoreceptors contain two functionally dissimilar inositol triphosphate-induced calcium release mechanisms.
Injections of inositol 1,4,5 triphosphate (InsP3) into Limulus ventral photoreceptors give rise to a rapid depolarization and an elevation of intracellular calcium concentration (Cai). This response to InsP3 is followed by a period of desensitization that persists as long as Cai remains elevated (feedback inhibition). Limulus ventral photoreceptors have two types of lobe: a light-sensitive rhabdomeric lobe (R lobe), and a light-insensitive arhabdomeric lobe (A lobe). Evidence showing the presence of feedback inhibition has been so far demonstrated only in the R lobe. In this study, simultaneous measurements of Cai were made using aequorin and double-barreled calcium-sensitive electrodes in each type of lobe. We carefully checked the location of the R lobe and A lobe by scanning a microspot of light across the whole photoreceptor. We then inserted a double-barreled calcium-sensitive microelectrode with InsP3 in either type of lobe. In the R lobe, injections of InsP3 led to a large Cai increase, a rapid depolarization and feedback inhibition; a brief flash of light induced a rapid depolarization and a Cai increase measured by both aequorin and the calcium-sensitive electrode. In the A lobe, injection of InsP3 led to an increase in Cai measured by the calcium-sensitive electrode but to no depolarization or aequorin luminescence. Further there was no evidence of feedback inhibition in the A lobe; the elevation of Cai caused by the first injection did not desensitize the photoreceptor to a second injection of InsP3 3 s later. To verify that the aequorin and the cell membrane respond to an increase in Cai, we presented a brief flash of light. Following a uniform illumination, there is indeed a typical large luminescence increase and a receptor potential. The calcium-sensitive electrode measures a small and slow Cai increase because its tip is located in the A lobe and it is measuring Ca2+ diffusing from the R lobe. Our observation that the InsP3-induced Cai increase in the A lobe is not apparently accompanied by a subsequent desensitization to InsP3 may suggest that there are more than one type of InsP3 receptor in the same cell. Alternatively, the InsP3 receptor could be the same but some additional factor, which confers feedback inhibition, could be missing in the A lobe.


Optimization and validation method to evaluate the residues of β-lactams and tetracyclines in kidney tissue by UPLC-MS/MS.
Methods are validated by a process that defines the analytical requirements and confirms that the investigated method is capable of performing consistently. A quantitative and confirmatory method for determining the presence of β-lactam and tetracycline multiresidues in avian, bovine, equine, and swine kidney tissues using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed, optimized, and validated. Analytes were extracted from the kidneys by a mixture of water and acetonitrile, and the extract was then purified with hexane and C18 (dispersive phase). The method was evaluated by the following parameters: linearity, matrix effect, specificity, decision limits (CCα), detection capability (CCβ), accuracy, precision, trueness, limits of detection (LOD), limits of quantification (LOQ), and robustness. The validated method presented a broad linear study range and significant matrix effect. The limit of detection (LOD) was defined from 2.5 to 25.0 µg kg(-1), and the limit of quantification (LOQ) was defined from 5.0 to 50.0 µg kg(-1) for individual analytes. The resultant recovery values ranged from 98.1% to 107.3% in repeatability conditions and from 95.2% to 106% under intralaboratory reproducibility conditions for the studied analytes. It was concluded that the performance parameters demonstrated total method adequacy for detecting and quantifying β-lactam and tetracycline residues in swine, equine, bovine, and avian kidneys.


Male Mating Tactics in Captive Rhesus Macaques (Macaca mulatta): The Influence of Dominance, Markets, and Relationship Quality.
Male mating success in a multimale-multifemale group can depend on several variables: body condition, dominance, coalitions, "friendship," or an exchange of services for mating access. Exchange patterns may also be determined by market effects or social relationships. We studied the mating tactics of males in a captive, multimale-multifemale group of rhesus macaques and the resulting patterns of mating and paternity to determine the influence of dominance rank, mating markets, and relationship quality on their mating tactics. Male rank was positively related to the total number of copulations and the number of mating partners, but did not explain male mating distribution completely. Moreover, male fertilization success was not related to male rank. Males did not exchange grooming for mating access on the same day and neither the supply nor the rank (as a proxy for quality) of receptive females affected the amount of male grooming, suggesting that market effects did not explain male mating access. However, there was a positive correlation between long-term grooming patterns of both males and females and mating access, indicating that social relationships were important for male mating access. Paternity data revealed that these social relationships were also important for male reproductive success. We conclude that both male rank and male-female "friendship" determined male mating access in these rhesus macaques, but that "friendship" was more important in determining paternity, emphasizing the importance of intersex social bonds in male mating success in multimale primate societies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10764-011-9552-5) contains supplementary material, which is available to authorized users.


Functional alterations induced by fusarium T-2 toxin in Madin-Darby bovine Kidney (MDBK) and primary fetal bovine Kidney (PFBK) cultures.
We recently reported that primary fetal bovine Kidney (PFBK) cells were consistently more sensitive to the cytotoxic effects of fusarium T-2 toxin than Madin-Darby bovine kidney (MDBK) cells in culture. The present report examined the influence of T-2 on selected biochemical parameters of these two culture types. T-2 toxin inhibited incorporation of labeled thymidine, uridine, and leucine in both culture types; at lower concentrations of the toxin, PFBK cells were affected to a greater extent than MDBK cells. T-2 toxin inhibited both the transport of thymidine as well as thymidine incorporation into macromolecules in MDBK cells during initial periods, but did not affect uridine incorporation. The cellular enzymes, K(+)- dependent phosphatase and succinic dehydrogenase were inhibited in MDBK but not in PFBK cultures; acid phosphatase was not influenced in either culture types. In a cell-free system none of the above enzymes were affected by T-2 until the toxin concentration exceeded 10(-5)M.


Treating childhood shyness and related behavior: empirically evaluated approaches to promote positive social interactions.
Behavioral and cognitive-behavioral strategies, including exposure, social skills training, and peer-mediated approaches, used to treat childhood shyness and related impairments are described. In addition, relevant outcome studies published within the past 20 years are evaluated, and limitations regarding the generalization, maintenance, and social validity of the reported treatment gains are addressed. Although the interventions reviewed have demonstrated short-term merit in ameliorating social and emotional impairments, such as problematic peer relations and internalizing difficulties, there currently is a lack of evidence to support the social validity and long-term generalization and maintenance of such behavioral gains. Thus, recommendations for future research are made, including the need to (a) assess the social validity of treatment outcomes, (b) utilize important socialization agents (e.g., parents, teachers, peers), and (c) conduct prevention research and longitudinal outcome studies.


High-performance liquid chromatographic evaluation of PCF 39, a new immunomodulator agent.
An high-performance liquid chromatographic analysis of PCF 39, N2-[5-(hypoxanthin-9-yl)pentyloxycarbonyl]-L-arginine, with ultraviolet detection, has been devised and validated. The main pharmacokinetic results encountered for rats treated intravenously with PCF 39 at a dose of 100 mg/kg are described.


Impaired thymopoiesis in interleukin-7 receptor transgenic mice is not corrected by Bcl-2.
Murine thymocytes down-regulate IL-7 responsiveness following beta-selection and reacquire sensitivity after positive selection. To assess the potential consequences of IL-7 signaling during this phase of development, transgenic IL-7 receptor alpha (IL-7Ralpha) mice were evaluated for IL-7 responsiveness as gauged by STAT-5 phosphorylation. Transgenic IL-7Ralpha expression increased the percentage of thymocytes responsive to IL-7 yet resulted in a decrease in total thymic cellularity. Aberrant thymocyte development in transgenic mice was first manifested by a reduction of DN3 thymocytes that correlated with lower Bcl-2 expression. Surprisingly, transgenic restoration of Bcl-2 expression did not correct thymic hypocellularity induced by IL-7Ralpha overexpression. These findings demonstrate that failure to appropriately downregulate IL-7Ralpha expression interferes with thymocyte development past the pro-T stage resulting in significantly lower levels of mature thymocytes.


Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract.
To study glial cell line-derived neurotrophic factor (GDNF) concentrations in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). GDNF was studied in AH, LF, and BS in 47 patients with age-related cataract, and 30 patients with POAG combined with cataract (one eye in each person). AH was sampled during cataract surgery. GDNF concentration (pg/ml) in patients with POAG and cataract was lower than in cataract-only patients (p<0.001), both in AH (46.3±31.1 versus 88.9±46.9) and in LF (222±101 versus 344±134). The difference was not significant for the GDNF concentration in BS (194±56 versus 201±45). In the earlier (early and moderate) stages of POAG, compared to later (advanced and severe) stages, GDNF concentration was significantly lower in LF (176±99 versus 258±91; p = 0.027) and in BS (165±42 versus 217±55; p = 0.017), while GDNF concentration in AH showed an insignificant difference (40.0±25.7 versus 51.1±34.7). In patients with POAG, GDNF concentration in LF and BS was inversely correlated with the Humphrey visual field index: Pearson's correlation coefficient r = -0.465 (p = 0.01) for LF and r = -0.399 (p = 0.029) for BS. When compared to the cataract group, patients in the earlier stages of POAG showed significantly lower GDNF concentrations in all studied biologic fluids. Compared to patients with cataract only, GDNF levels are lower in the AH and LF of patients with POAG and cataract, especially at earlier stages of the disease (at these stages, the GDNF level in BS is also lower). At earlier stages of POAG, compared to later stages, GDNF content is lower in LF and BS. These data could serve as a reason for the therapeutic use of GDNF in patients with POAG.