Optimizing Tube Precurvature to Enhance Elastic Stability of Concentric Tube Robots.
Robotic instruments based on concentric tube technology are well suited to minimally invasive surgery since they are slender, can navigate inside small cavities and can reach around sensitive tissues by taking on shapes of varying curvature. Elastic instabilities can arise, however, when rotating one precurved tube inside another. In contrast to prior work that considered only tubes of piecewise constant precurvature, we allow precurvature to vary along the tube's arc length. Stability conditions for a planar tube pair are derived and used to formulate an optimal design problem. An analytic formulation of the optimal precurvature function is derived that achieves a desired tip orientation range while maximizing stability and respecting bending strain limits. This formulation also includes straight transmission segments at the proximal ends of the tubes. The result, confirmed by both numerical and physical experiment, enables designs with enhanced stability in comparison to designs of constant precurvature.


[One stage operation for aneurysm of the diverticulum of the ductus arteriosus and coronary artery bypass grafting].
Aneurysm of the diverticulum of the ductus arteriosus in the adult is rare. One stage operation for aneurysm of the diverticulum of the ductus arteriosis and coronary artery bypass grafting (CABG) is reported. A 61-year-old man was admitted for diagnosis of thoracic aneurysm on chest X-ray and CT. Chest CT scan showed an aneurysm above the left main pulmonary artery. An aortography showed the left vertebral artery originated directly from the aortic arch and a saccular aneurysm arising from the aortic isthmus and lesser curvature of the aortic arch. Coronary arteriography showed 75% stenosis at the right coronary artery (seg. #1) and 75% stenosis at the left anterior descending artery. Operation was performed through a median sternotomy. The aneurysm of 6 to 3 cm was located between the aortic isthmus and left pulmonary artery. Ascending aorta and right atrium were used to institute cardiopulmonary bypass (CPB). CABG (LITA to #7, SVG to #4 PD) was performed. Arterial cannulation was then switched to the left femoral artery. The proximal aorta was cross-clamped between the left vertebral artery and the left subclavian artery under the partial CPB, and the distal aorta was occluded with a occulusive balloon catheter via the right femoral artery. The selective left axillar artery cannulation was performed to perfuse LITA. The aneurysm was resected and closed with a patch. His post-operative course was uneventful.


Obituary: Ira Herskowitz.
Jasper Rine pays tribute to a distinguished career spanning several fields and a personality that was a legend among the many great teachers at UCSF.


Laser-assisted lung metastasectomy: a systematic review.
Laser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details, indications and outcomes of LAR have not been extensively reviewed. We conducted a systematic literature search to identify all original articles reporting on LAR of pulmonary metastases. All relevant outcomes, including morbidity rate, R0 rate, pulmonary function tests, overall- (OS) and relapse-free survival (RFS) rates were collected. Additionally, a comparison between outcomes obtained by laser-assisted and conventional resection techniques was provided. Of 2629 articles found by the initial search, 12 were selected for the systematic review. Following LAR, the R0 rate ranged between 72 and 100% and the morbidity rate ranged from 0 to 27.5%. The postoperative decline in forced expiratory volume in 1 s varied between 3.4 and 11%. Median OS and RFS were 42-77.6 months and 9-34.1 months, respectively. Compared with patients treated by other resection techniques, patients treated by LAR frequently had a higher number of metastases and a higher rate of bilateral disease. Despite this, no significant differences were observed in R0 rate, morbidity rate, and median OS rate, while only 1 study found a lower RFS rate in the LAR cohort. Although selection bias limits the comparability of outcomes, the findings of this review suggest that LAR is a valid alternative to conventional procedures of lung metastasectomy. The main difficulties of this technique consist in the adoption of a video-assisted thoracoscopic approach, and in the pathologic assessment of resection margins.


New perspectives to meet nutrition information needs of the older consumer.
Extension of life and improvement of the quality of the later years present significant challenges to health care providers, researchers, and educators. The "new older persons" population is, indeed, a segment of society that has never existed before. Many traditional approaches to health education will continue to be effective, but newer techniques must be explored. Changing circumstances mandate an openness of mind rarely before required of the health community. New alliances, based on the common goal of helping older persons enjoy life and mutual respect, founded on true professionalism, must be forged. Vital roles and responsibilities exist for both "hard" and "soft" scientists, for industry as well as for government. Most important, however, is establishing an active role for the individual older consumer.


Modulation of [35S]TBPS binding by ligands with preferential affinity for benzodiazepine BZ1 sites in the cerebral cortex of newborn and adult rats.
The present study was designed to compare the allosteric coupling between the Cl- channel of the GABAA receptor and the different benzodiazepine recognition site subtypes (BZ sites) in the cerebral cortex of newborn (5-day-old) and adult rats (90-day-old). To this aim, we reexamined the heterogeneity of cortical GABAA receptors in self- and cross-competition binding experiments using [3H]flunitrazepam and two ligands with higher affinity for benzodiazepine BZ1 sites relative to benzodiazepine BZ2 sites, the triazolopyridazine 3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo [4,3-b] pyridazine (CL 218,872) and the imidazopyridine N,N,6-trimethyl-2-(4-methylphenyl)-imidazo[1,2-a]-pyridine-3-acetamide hemitartrate (zolpidem). Benzodiazepine BZ1 sites accounted for 52% of the total number of binding sites in adult rats, but were not detected in newborn rats. On the other hand, two classes of benzodiazepine BZ2 sites with high and low affinity for zolpidem were present in newborn and adult rats. These sites were designated as benzodiazepine BZ2H (high affinity for zolpidem, Kd approximately 150 nM) and benzodiazepine BZ2L (low affinity for zolpidem, Kd approximately 3000 nM). High densities of benzodiazepine BZ2H sites were measured in both newborn and adult rats (75% and 41% of the total number of [3H]flunitrazepam binding sites, respectively), whereas benzodiazepine BZ2L sites accounted for 25% and 7% of the total number of cortical sites in neonates and adults, respectively. Flunitrazepam, CL 218,872 and zolpidem inhibited in a concentration-dependent manner the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to the convulsant site of cortical GABAA receptors in newborn and adult rats. The IC50 for flunitrazepam was about 3-fold greater in adults than in neonates. This rightward shift in the concentration-response curve may be due to a decrease with age in the intrinsic efficacy of flunitrazepam. In contrast, CL 218,872 and zolpidem were 4-fold more potent at inhibiting [35S]TBPS binding in adult rats relative to neonates. The different affinities of CL 218,872 and zolpidem for benzodiazepine BZ1 and BZ2 receptors may account, at least in part, for the age-related changes in their inhibitory potencies. These results demonstrate that benzodiazepine BZ2 sites mediate the modulation of [35S]TBPS binding by benzodiazepine recognition site ligands in the cerebral cortex of newborn rats. Further, benzodiazepine BZ2 sites may be involved in the inhibition of [35S]TBPS binding by flunitrazepam, CL 218,872 and zolpidem in the cerebral cortex of adult rats.


Within-session and between-session effects of auditory biofeedback training on center of pressure location during gait in patients with chronic ankle instability.
To establish preliminary gait training dosage parameters for patients with chronic ankle instability (CAI) by determining the within-session and between-session effects of auditory biofeedback training on center of pressure (COP) location during gait. Observational Longitudinal. Laboratory. 19 participants with CAI, 8 participants who did not receive auditory biofeedback (NoFeedback group) and 11 participants who did receive auditory biofeedback (AuditoryFeedback group) over an 8-session 2-week intervention. COP location was measured at the start and at each 5-min interval during treadmill walking across all eight 30-min training sessions. The AuditoryFeedback group had significant within-session lateral-to-medial shifts in COP location during only session-1 at the 15-min (45% of stance; peak mean difference = 4.6 mm), 20-min (35% and 45%; 4.2 mm), and 30-min time intervals (35% and 45%; 4.1 mm). Furthermore, the AuditoryFeedback group had significant between-session lateral-to-medial shifts in COP location at session-5 (35-55% of stance; 4.2 mm), session-7 (35%-95%; 6.7 mm), and session-8 (35%-95%; 7.7 mm). The NoFeedback group had no significant changes in COP location within-sessions or between-sessions. Participants with CAI who received auditory biofeedback during gait needed an average of 15-min during session-1 to meaningfully shift their COP location medially and 4-sessions before retaining the adapted gait pattern.


The topography of rat submandibular gland parenchyma as observed with S.E.M.
The parenchymal components of rat submandibular gland were examined by scanning electron microscopy after removal of the stromal connective tissue by acid hydrolysis and/or enzymatic digestion. Secretory acini have polymorphous topographies but usually consist of three to five truncated lobes emanating from a common hilus. They have a mean volume of about 33,000 micrometers3. Myoepithelial cells are associated with the deeper acini of the gland where they cover congruent to 54% of the surface area of their allied acini. Each flattened myoepithelial cell has a central perikaryon that gives rise to four or five broad primary processes that bifurcate two or three times to produce a total complement of 20 to 40 terminal processes per cell, each 0.5 micrometer to 1.7 micrometers wide. The terminal processes of adjacent myoepithelial cells tend to slightly overlap and to attach to each other by desmosomes forming a network over adjacent acini. The components of the duct system are examined and each characterized by salient features as observed with the SEM.


A meta-analysis of white matter changes in temporal lobe epilepsy as studied with diffusion tensor imaging.
Diffusion tensor imaging (DTI) is used increasingly to study white matter integrity in people with temporal lobe epilepsy (TLE). Most studies report fractional anisotropy (FA) decrease and mean diffusivity (MD) increase in multiple white matter regions. The disturbance of white matter integrity varies across studies and between regions. We aimed to obtain a more consistent estimate of white matter diffusion characteristics and relate these to the distance from the seizure focus. Studies comparing diffusion characteristics of people with epilepsy with those of healthy controls were systematically reviewed and quantified using random and mixed effects meta analysis. In addition to the overall meta-analysis, pooled FA and MD differences were determined per hemisphere and white matter category separately. We included 13 cross-sectional studies. The pooled FA difference for all white matter was -0.026 (95% confidence interval [CI] -0.033 to -0.019) and MD difference was 0.028 × 10(-3) mm(2)/s (95% CI 0.015-0.04). FA was reduced significantly in people with TLE compared with healthy controls in both ipsilateral (mean difference -0.03) and contralateral white matter (-0.02). MD was significantly increased ipsilaterally and contralaterally. MD differed significantly between white matter connected to the affected temporal lobe and remote white matter. The meta-analysis provides a better estimation of the true diffusion characteristics. White matter structural integrity in TLE is disturbed more severely in the ipsilateral than in the contralateral hemisphere, and tracts closely connected with the affected temporal lobe are most disturbed. The exact underlying mechanisms remain to be elucidated.


Retrospective multi-institutional study of radiotherapy for intracranial non-germinomatous germ cell tumors.
The treatment outcome of 24 patients with pathologically-proven non-germinomatous germ cell tumor was retrospectively investigated to determine the effectiveness of radiotherapy. The patients were divided into three groups as follows: group 1, five patients with mature teratoma with or without germinoma; group 2, six patients with immature teratoma with or without germinoma; group 3, 13 patients with other highly malignant tumors. The overall actuarial survival and relapse-free rates at 5 years were 82% and 59%, respectively, with a median follow-up period of 62 months. The actuarial relapse-free rate at 5 years was 100% for group 1, 63% for group 2 and 44% for group 3. There was no difference in the relapse-free rates between total resection and partial resection. Usage of chemotherapy was adversely related to survival probably due to selection bias. No local failure was observed with 10 Gy or more for group 1,40 Gy or more for group 2 and 54 Gy or more for group 3. In groups 1 and 2, there was no spinal relapses without craniospinal irradiation. In group 3, three of eight patients who did not receive craniospinal irradiation and none of five patients who received craniospinal irradiation experienced spinal relapse. In conclusion, highly malignant GCTs show a high incidence of spinal metastasis and craniospinal irradiation may reduce the risk of spinal metastasis. Radiation dose and volume are to be determined according to the histopathological aggressiveness.


[Phorbol-12-myristate-13-acetate prevents the inhibitory effect of A23187 on erythroid differentiation of K562 cells induced by dimethylsulfoxide].
The differentiating effect of DMSO on K562 cells was studied against the background of pretreatment of the cells by the modulators of activities of protein kinase C and Ca signaling, phorbol 12-myristate 13-acetate, and ionophore A23187. The 2-hour pretreatment of K562 cells with A23187 (1 microM), rather than phorbol 12-myristate 13-acetate (0.1 microM), led to inhibition of the differentiating effect of DMSO (0.1%) during the subsequent four days of incubation. When the cells were pretreated jointly with A23187 and phorbol 12-myristate 13-acetate, the DMSO-induced erythroid differentiation was restored. Analysis of the DNA-degrading effect of the reagents used on K562 cells by fluorescent dyes under the same conditions suggests that this activity is induced in the presence of DMSO in the cells pretreated with a combination of phorbol 12-myristate 13-acetate and A23187 or without pretreatment.


Estimation of left ventricular filling pressure by Doppler echocardiography in dogs with pacing-induced heart failure.
Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. Five male hound dogs. Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160-180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R(2)= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing.


The Trier Social Stress Test for Groups (TSST-G): A new research tool for controlled simultaneous social stress exposure in a group format.
Psychological stress is an ubiquitous challenge across human cultures affecting mental and physical health. Recent evidence indicates that performance tasks combining elements of socio-evaluative threat and uncontrollability elicit reliable stress responses. The Trier Social Stress Test (TSST) is the most frequently used psychological protocol in stress research; however, to date it has only been available in a single-subject version. In particular, there is an increasing need in several emerging research fields such as stress research or social neurosciences for a standardized research tool to expose relatively large groups of subjects to controlled simultaneous stress. In search of a laboratory stressor that allows simultaneous stress exposure in a group format, we exposed a total of 25 healthy male participants to the Trier Social Stress Test for Groups (TSST-G; public speaking and mental arithmetic tasks in front of a panel of two evaluators in groups of six participants) and a specific control condition. Results showed that the TSST-G induced significant increases in cortisol, heart rate, and psychological stress responses. The TSST-G provides a novel, effective, and economical protocol for experimental paradigms requiring simultaneous stress induction in multiple participants.


The holmium:YAG laser lithotripsy-a non-invasive tool for removal of midsize stones of major salivary glands.
Incorporeal lithotripsy by using holmium:YAG laser has been recently successfully spread and used in the treatment of urolithiasis. Although this method is not as common in salivary gland surgery, it is also recommended for endoscopic treatment of sialolithiasis. In this study, we decided to analyse effectiveness of holmium:YAG laser method among patients with midsize stones as the treatment in this particular population is still not determined and remains in dispute. Thus, the primary aim of the study is a prospective, complex analysis of incorporeal holmium:YAG laser lithotripsy effectiveness and safety in patients suffering from sialolithiasis. The examined group consisted of 32 consecutive patients, 17 female (53%) and 15 male (47%). The average age was 42 (age range 22-70). In our series, sialoendoscopy with intraductal lithotripsy was performed in patients with wide range of stone's diameter (3 to 10 mm). The calculi were removed with foreign body forceps or retrieval basket, after stone fragmentation with holmium:YAG laser. The power of the laser during surgery was set at 2.5 to 3.5 W. One shot energy equalled 0.5-0.7 J with frequency of 5 Hz. The bivariate Pearson Correlation and a point-biserial correlation were used to analyse the data. Total success rate of holmium:YAG laser lithotripsy in this consecutive group was equal to 90% and efficacy in the group with excluded cases when endoscopic approach difficulties were experienced (stone not visible) reached 93%. The long-term follow-up revealed that in 26 patients (84%), complete recovery was achieved. Two patients developed Wharton's duct stenosis and one Stensen's duct orifice stenosis (9.5%), of whom one required reoperation. Two patients eventually underwent total excision of submandibular gland. Sialoendoscopy combined with incorporeal laser-assisted lithotripsy proved to be effective and safe method for treatment of sialothiasis with midsize stones (4-8 mm) in population of clinic. Even taking into account the prevalence of complications associated with holmium:YAG laser, it is still safer alternative compared to open surgery where there is a significant risk of the bleeding, wound infection or injury of the facial nerve.


Membrane structure and internalization dynamics of human Flower isoforms hFWE3 and hFWE4 indicate a conserved endocytic role for hFWE4.
Human Flower (hFWE) isoforms hFWE1-4 are putative transmembrane (TM) proteins that reportedly mediate fitness comparisons during cell competition through extracellular display of their C-terminal tails. Isoform topology, subcellular localization, and duration of plasma membrane presentation are essential to this function. However, disagreement persists regarding the structure of orthologous fly and mouse FWEs, and experimental evidence for hFWE isoform subcellular localization or membrane structure is lacking. Here, we used AlphaFold2 and subsequent molecular dynamics-based structural predictions to construct epitope-tagged hFWE3 and hFWE4, the most abundant human isoforms, for experimental determination of their structure and internalization dynamics. We demonstrate that hFWE3 resides in the membrane of the endoplasmic reticulum (ER), while hFWE4 partially colocalizes with Rab4-, Rab5-, and Rab11-positive vesicles as well as with the plasma membrane. An array of imaging techniques revealed that hFWE4 positions both N- and C-terminal tails and a loop between second and third TM segments within the cytosol, while small (4-12aa) loops between the first and second and the third and fourth TM segments are either exposed to the extracellular space or within the lumen of cytoplasmic vesicles. Similarly, we found hFWE3 positions both N- and C-terminal tails in the cytosol, while a short loop between TM domains extends into the ER lumen. Finally, we demonstrate that hFWE4 exists only transiently at the cell surface and is rapidly internalized in an AP-2- and dynamin-1-dependent manner. Collectively, these data are consistent with a conserved role for hFWE4 in endocytic processes.


A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma.
Conditionally replicating adenoviruses (CRADs) take advantage of tumor-specific characteristics for preferential replication and subsequent oncolysis of cancer cells. The antitumor effect is determined by the capability to infect tumor cells. Here, we used RGDCRADcox-2R, which features the cyclooxygenase-2 promoter for replication control and an integrin binding RGD-4C motif for enhanced infectivity of ovarian cancer cells. RGDCRADcox-2R replicated in and killed human ovarian cancer cells effectively, while the replication in nonmalignant cells was low. Importantly, the therapeutic efficacy, as evaluated in an orthotopic model of peritoneally disseminated ovarian cancer, was significantly improved and toxicity was lower than with a wild-type virus. Thus, this CRAD could be tested for treatment of ovarian cancer in humans.


Lethal and estrogenic effects of 4-nonylphenol in the cockle Cerastoderma glaucum.
The lethal and sublethal effects of the xenoestrogen 4-nonylphenol (NP) were evaluated in the cockle Cerastoderma glaucum. In a 96-h lethality test, bivalves were exposed to 0, 0+ acetone, 0.19, 0.38, 0.75, 1.5 and 3.0 mg NP/l. The 96-h LC(50) value was 0.3mg NP/l. No mortality was observed at 0.1 mg NP/l. The potential estrogenicity of NP was studied in both sexually undifferentiated (resting phase) and differentiated (pre-spawning phase) cockles, exposed for 7 and 14 days to 0, 0+ acetone, 0.0125, 0.025, 0.05, and 0.1 mg NP/l. Vitellogenin (Vg)-like protein levels were determined in both haemolymph and digestive gland by the alkali-labile phosphate (ALP) assay. In the resting phase, exposure for 7 days to 0.1 mg NP/l resulted in significant increases in ALP in both haemolymph and digestive gland, compared with controls. A significant increase was also observed in digestive gland of animals exposed to 0.0125 mg NP/l-exposed animals. After 14 days of exposure, haemolymph ALP levels were significantly increased in exposed animals at all NP concentrations tested, whereas no difference was recorded in digestive gland. In the pre-spawning phase, exposure for 7 days to NP significantly increased ALP levels in haemolymph from males exposed at all NP concentrations tested, whereas no significant variations were found in haemolymph from females. NP (0.05 and 0.1 mg/l) was also shown to increase ALP concentrations significantly in digestive gland of males, but not in those of females. Likewise, after 14 days' exposure, ALP levels significantly increased in haemolymph from males only at 0.1 mg NP/l. Conversely, NP caused significant increases in ALP levels in digestive gland from both males (at all NP concentrations tested) and females (at 0.025 and 0.1 mg NP/l). These results demonstrate that NP induces Vg synthesis in C. glaucum. Interestingly, males were more responsive to NP than females.


Patients' experience of asthma control and clinical guidelines: perspectives from a qualitative study.
Clinical guidelines consider the concept of 'asthma control' as the primary goal of asthma treatment. This study aimed to explore patients' views of concepts that are important for understanding and evaluating asthma control. Patients with mild to severe asthma in four countries completed the Asthma Control Questionnaire (ACQ) and discussed their experiences in focus groups. Clinicians evaluated patients' levels of asthma control based on Global Initiative for Asthma (GINA) guidelines. Clinician- and questionnaire-based ratings of asthma control were compared. Thematic analysis was used to identify key concepts from focus group transcripts. The sample consisted of 55 patients. Classification of asthma control, based on the ACQ, was consistent with clinician rating in 28 cases (51%). In focus groups, patients discussed concepts related to symptoms, asthma attacks (exacerbations), activity limitations, panic/fear, tiredness, sleep disturbances (nocturnal awakening and difficulty falling asleep), and rescue medication use when describing asthma control. Clinical guidelines also focus on symptoms, activity limitations, rescue medication use, and exacerbations but, in addition include lung function parameters. Guidelines do not take into account asthma-related panic/fear or tiredness and sleep disturbances beyond nocturnal awakening. The results of this study suggest that patients' understanding of asthma control extends beyond the usual clinical manifestation of respiratory symptoms and lung function. This may have implications for clinical practice, for setting and achieving the goals of asthma control as well as for evaluation of treatments for asthma from the patients' perspective.


Utilizing a reductionist model to study host-microbe interactions in intestinal inflammation.
The gut microbiome is altered in patients with inflammatory bowel disease, yet how these alterations contribute to intestinal inflammation is poorly understood. Murine models have demonstrated the importance of the microbiome in colitis since colitis fails to develop in many genetically susceptible animal models when re-derived into germ-free environments. We have previously shown that Wiskott-Aldrich syndrome protein (WASP)-deficient mice (Was-/-) develop spontaneous colitis, similar to human patients with loss-of-function mutations in WAS. Furthermore, we showed that the development of colitis in Was-/- mice is Helicobacter dependent. Here, we utilized a reductionist model coupled with multi-omics approaches to study the role of host-microbe interactions in intestinal inflammation. Was-/- mice colonized with both altered Schaedler flora (ASF) and Helicobacter developed colitis, while those colonized with either ASF or Helicobacter alone did not. In Was-/- mice, Helicobacter relative abundance was positively correlated with fecal lipocalin-2 (LCN2), a marker of intestinal inflammation. In contrast, WT mice colonized with ASF and Helicobacter were free of inflammation and strikingly, Helicobacter relative abundance was negatively correlated with LCN2. In Was-/- colons, bacteria breach the mucus layer, and the mucosal relative abundance of ASF457 Mucispirillum schaedleri was positively correlated with fecal LCN2. Meta-transcriptomic analyses revealed that ASF457 had higher expression of genes predicted to enhance fitness and immunogenicity in Was-/- compared to WT mice. In contrast, ASF519 Parabacteroides goldsteinii's relative abundance was negatively correlated with LCN2 in Was-/- mice, and transcriptional analyses showed lower expression of genes predicted to facilitate stress adaptation by ASF519 in Was-/-compared to WT mice. These studies indicate that the effect of a microbe on the immune system can be context dependent, with the same bacteria eliciting a tolerogenic response under homeostatic conditions but promoting inflammation in immune-dysregulated hosts. Furthermore, in inflamed environments, some bacteria up-regulate genes that enhance their fitness and immunogenicity, while other bacteria are less able to adapt and decrease in abundance. These findings highlight the importance of studying host-microbe interactions in different contexts and considering how the transcriptional profile and fitness of bacteria may change in different hosts when developing microbiota-based therapeutics. Video abstract.


Revealing low-temperature plasma efficacy through a dose-rate assessment by DNA damage detection combined with machine learning models.
Low-temperature plasmas have quickly emerged as alternative and unconventional types of radiation that offer great promise for various clinical modalities. As with other types of radiation, the therapeutic efficacy and safety of low-temperature plasmas are ubiquitous concerns, and assessing their dose rates is crucial in clinical settings. Unfortunately, assessing the dose rates by standard dosimetric techniques has been challenging. To overcome this difficulty, we proposed a dose-rate assessment framework that combined the predictive modeling of plasma-induced damage in DNA by machine learning with existing radiation dose-DNA damage correlations. Our results indicated that low-temperature plasmas have a remarkably high dose rate that can be tuned by various process parameters. This attribute is beneficial for inducing radiobiological effects in a more controllable manner.


Seasonality of birth in epilepsy: a Danish study.
A recent British epidemiological study, having found that the seasonality of birth in a large epileptic sample was significantly different from that of the general population, has pointed to neurodevelopmental disruption as the likely mechanism to cause at least part of the epilepsies of unknown aetiology. The aim of this study is to replicate the British study using a large Danish sample. The population studied is composed by all the 50,886 patients discharged from Danish Hospitals, with a diagnosis of epilepsy, in the period from 1977 to 1993. The seasonal pattern of birth in this sample has been compared, using regression methods, with all the live births in Denmark. The results were strikingly similar to the British study, with a deficit of epileptic births in September and an excess during the winter months. This study seems to confirm the seasonal presence in the environment of an aetiological factor(s) for epilepsy which acts in the perinatal period disrupting the neurodevelopment.


The effect of radiolabeling of human fibrinogen on its adsorption behaviour on a polystyrene surface.
Human fibrinogen (HFB) was labeled with different radioactive labels (Technetium -99m and iodine -125) in various ways. Characterization by chromatographic and electrophoretic methods did not show differences between the labeled and the nonlabeled proteins. The effect of the label and the labeling method on the adsorption behaviour of 99mTc and 125I labeled HFB at a polystyrene surface was investigated. In all cases labeled HFB showed preferential adsorption as compared to nonlabeled HFB. The preferential adsorption was expressed in terms of a factor ø (van der Scheer et al. 1978a), which will be 1, when no preferential adsorption occurs. 99mTc - and 125I - HFB showed ø values from 1.48 - 1.88. It is concluded that only meaningful adsorption experiments with labeled proteins can be performed when the possible occurrence of preferential adsorption has been investigated by appropriate methods. The results of prior work on protein adsorption at biomaterials using radiolabeled proteins have to be reconsidered.


Inflammation-induced left ventricular fibrosis is partially mediated by tumor necrosis factor-α.
To determine the mechanisms of inflammation-induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF-α) in a model of systemic inflammation. Seventy Sprague-Dawley rats were divided into three groups: the control group, the collagen-induced arthritis (CIA) group, and the anti-TNF-α group. Inflammation was induced in the CIA and anti-TNF-α groups. Following the onset of arthritis, the anti-TNF-α group received the TNF-α inhibitor, etanercept, for 6 weeks. LV geometry and function were assessed with echocardiography. Circulating inflammatory markers were measured by ELISA and LV gene expression was assessed by comparative TaqMan® polymerase chain reaction. The LV relative gene expression of pro-fibrotic genes, transforming growth factor β (TGFβ) (p = 0.03), collagen I (Col1) (p < 0.0001), and lysyl oxidase (LOX) (p = 0.002), was increased in the CIA group compared with controls, consistent with increased relative wall thickness (p = 0.0009). Col1 and LOX expression in the anti-TNF-α group were similar to controls (both, p > 0.05) and tended to be lower compared to the CIA group (p = 0.06 and p = 0.08, respectively), and may, in part, contribute to the decreased relative wall thickness in the anti-TNF-α group compared to the CIA group (p = 0.03). In the CIA group, the relative gene expression of matrix metalloproteinase 2 (MMP2) and MMP9 was increased compared to control (p = 0.04) and anti-TNF-α (p < 0.0001) groups, respectively. Chronic systemic inflammation induces fibrosis and dysregulated LV extracellular matrix remodeling by increasing local cardiac pro-fibrotic gene expression, which is partially mediated by TNF-α. Inflammation-induced LV diastolic dysfunction is likely independent of myocardial fibrosis.


Emergency medicine in the Veterans Health Administration-results from a nationwide survey.
We describe emergency physician staffing, capabilities, and academic practices in US Veterans Health Administration (VHA) emergency departments (EDs). As part of an ongoing process improvement effort for the VHA emergency care system, VHA-wide surveys are conducted among ED medical directors every 3 years. Web-based surveys of VHA ED directors were conducted in 2013 on clinical operations and academic program development. We describe the results from the 2013 survey. When available, we compare responses with the previously administered survey from 2010. A total of 118 of 118 ED directors filled out the survey in 2013 (100% response rate). Respondents reported that 45.5% of VHA emergency physicians are board certified in emergency medicine, and 95% spend most their time in direct patient care. Clinical care is also provided by part-time (<0.5 full-time employee equivalent) emergency physicians in 59.3% of EDs. More than half of EDs (57%) provide on-site tissue plasminogen activator for acute ischemic stroke patients, and only 39% can administer tissue plasminogen activator 24 hours per day, 7 days per week. Less than half (48.3%) of EDs have emergency Obstetrics and Gynecology consultation availability. Most VHA EDs (78.8%) have a university affiliation, but only 21.5% participated in the respective academic emergency medicine program. Veterans Health Administration emergency physicians have primarily clinical responsibilities, and less than half have formal emergency medicine board certification. Despite most VHA EDs having university affiliations, traditional academic activities (eg, teaching and research) are performed in only 1 in 3 VHA EDs. Less than half of VHA EDs have availability of consulting services, including advanced stroke care and women's health.


Early Declines in Vaccine Type Pneumococcal Carriage in Children Less Than 5 Years Old After Introduction of 10-valent Pneumococcal Conjugate Vaccine in Mozambique.
Pneumococcal carriage is a precursor of invasive pneumococcal disease. Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in April 2013, using a 3-dose schedule without a booster. We evaluated PCV10 impact on pneumococcal carriage and colonization density by HIV status. We conducted 2 cross-sectional surveys (pre and post PCV10 introduction) among children 6 weeks to 59 months old. Participants included HIV-infected children presenting for routine care at outpatient clinics and a random sample of HIV-uninfected children from the community. We collected demographic data, vaccination history and nasopharyngeal swabs. Swabs were cultured and isolates serotyped by Quellung. We selected serotypes 11A, 19A and 19F for bacterial density analyses. We compared vaccine-type (VT) carriage prevalence from the pre-PCV10 with the post-PCV10 period by HIV status. Prevalence of VT carriage declined from 35.9% (110/306) pre already defined in the background. It should be pre-PCV (PCV) to 20.7% (36/174 fully vaccinated) post PCV (P < 0.001) in HIV-uninfected and from 34.8% (144/414) to 19.7% (27/137 fully vaccinated) (P = 0.002) in HIV-infected children. Colonization prevalence for the 3 serotypes (3, 6A, 19A) included in the 13-valent PCV but not in PCV10 increased from 12.4% (38/306) to 20.7% (36/174 fully vaccinated) (P = 0.009) among HIV- uninfected children, mainly driven by 19A; no significant increase was observed in HIV-infected children. VT carriage among unvaccinated children decreased by 30% (P = 0.005) in HIV-infected children, with no significant declines observed in HIV-uninfected children. Declines in VT carriage were observed in both HIV-uninfected and HIV-infected children after PCV10 introduction with an early signal of herd effect especially in HIV-infected children. Ongoing monitoring of increases in 19A carriage and disease is necessary.


A novel chitin-binding protein identified from the peritrophic membrane of the cabbage looper, Trichoplusia ni.
A novel midgut peritrophic membrane (PM) protein, TnPM-P42, was identified from the cabbage looper, Trichoplusia ni. TnPM-P42 was shown as a 42kDa protein by SDS-PAGE analysis and appeared to be associated with the PM throughout its entire length. In T. ni larvae, the midgut is the only tissue where TnPM-P42 could be detected during the feeding period of the larvae. TnPM-P42 has chitin-binding activity and is strongly associated with the PM, which is similar to the currently known peritrophin type PM proteins. However, TnPM-P42 represents a unique family of proteins distinctly different from the peritrophin type PM proteins in its sequence characteristics. TnPM-P42 does not contain the peritrophin domain which is present in all the currently known PM proteins, but instead has a chitin deacetylase-like domain. Sequence similarity search of the GenBank database did not result in identification of any known proteins with a significant overall sequence similarity to the TnPM-P42. However, expressed sequence tags (ESTs) from various arthropods were identified to code for proteins with high sequence similarities to TnPM-P42, indicating the presence of TnPM-P42 homologs in other arthropods. Consistent with the identification of various ESTs from arthropods, Western blot analysis demonstrated the presence of a TnPM-P42-like protein in the PMs from Heliothis virescens and Helicoverpa zea larvae. The sequence characteristics of TnPM-P42 indicate that TnPM-P42 represents a novel family of insect proteins. However, its biochemical and physiological functions require further investigation.


Monophasic Synovial Sarcoma of Tongue: A Rarest of Rare Case Scenario.
Synovial sarcoma is a rare tumour of head and neck. Primary synovial sarcoma of tongue is very uncommon. Based on morphology, it can be classified as classical biphasic variant, monophasic spindle cell variant, monophasic epithelial variant and poorly differentiated variant. The authors with an index case of 74 year old lady with monophasic spindle cell synovial sarcoma of oral tongue which is one of the rarest variants (our case is the 15th case reported of synovial sarcoma of the tongue and only the 3rd case in the world which had a monophasic histopathologic pattern) studied the morphology and described the disease entity in detail. She was treated with wide local excision of sarcoma followed by adjuvant radiotherapy.


Fluoro-substituted ketones from nitriles using acidic and basic reaction conditions.
Fluoro-substituted aliphatic nitriles are shown to undergo the Houben-Hoesch reactions with arenes in CF(3)SO(3)H to give fluoro-substituted ketones in good yields. The fluorine substituents appear to enhance the reactivities of the nitriles (and the nitrilium ion intermediates) compared to similar aliphatic nitriles. Fluoro-substituted ketones are also shown to be accessible through the reactions of organometallic reagents and fluoro-substituted nitriles.


Stromal networking: cellular connections in the germinal centre.
Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ. Further, distinct populations of stromal cells underpin the delicate spatial organization of immune cells within the germinal centre. Because of this, the interactions between immune cells and stromal cells in secondary lymphoid organs are fundamental to the germinal centre response. Herein we review how this unique relationship leads to effective germinal centre responses.


Enhanced Recovery After Surgery Programs for Laparoscopic Colorectal Resection May Not Need Thoracic Epidural Analgesia.
The aim of this study was to evaluate the necessity of thoracic epidural analgesia (TEA) as enhanced recovery after surgery (ERAS) programs for laparoscopic colorectal surgery (LC). We retrospectively compared between perioperative outcomes of patients who underwent LC with TEA (n=31) and with multimodal analgesia (MMA) (n=31). Furthermore, we also evaluated the patients' satisfaction by a questionnaire survey to the nurses. The only numeric rating scale (NRS) score on post-operative day (POD) 1 of the MMA group was significantly higher than that in the TEA group (p=0.002). In multivariate analysis, the factors that demonstrated significant correlation with hospital stay did not include analgesia. The 74% of the nurses felt equal or higher analgesic effect in the MMA group and interestingly, 84% of them answered that they would choose MMA if they were to undergo LC. TEA may not be necessary for ERAS in LC.


A convenient synthesis of cis and trans 4-tert-butoxycarbonyl-substituted cyclohexylglycine.
A novel synthesis of cis and trans substituted 4-tert-butoxycarbonyl cyclohexylglycines via asymmetric aminohydroxylation of vinyl styrene followed by reduction of the aromatic ring and subsequent oxidation is reported.


Hsp70 suppresses apoptosis in sympathetic neurones by preventing the activation of c-Jun.
The anti-apoptotic effects of heat-shock protein (Hsp70) were assessed in SCG neurones following nerve growth factor (NGF) withdrawal. The results showed that the virally mediated expression of Hsp70 mirrored the effects of the c-Jun-N-terminal kinase (JNK) binding domain (JBD) of JNK interacting protein (an inhibitor of JNK and c-Jun activation) and suppressed the phosphorylation of c-Jun. Preventing c-Jun transcriptional activity subsequently led to reduced cytochrome c release and prevented caspase activation as indicated by a decrease in poly (ADP-ribose) polymerase-1 (PARP) cleavage. Together, these results show that Hsp70 is a highly effective inhibitor of apoptosis in sympathetic neurones and that it mediates this effect primarily by suppressing c-Jun transcriptional signalling.


Role of nuclear medicine in chemotherapy of malignant lesions.
The major role of nuclear medicine in clinical oncology is in tumor imaging, which includes evaluating specific organs or the entire body for the presence of tumor. Nuclear medicine studies have been used clinically in the initial evaluation of the tumor extent and in the subsequent management of the cancer patient to assess response to treatment, to detect early relapse, and to assist in making decisions concerning follow-up treatment. Technetium-99m macroaggregated albumin perfusion study for intraarterial chemotherapy has been helpful in monitoring the catheter tip, providing a map of regional perfusion at the capillary level (tumor vascularity), evaluating the degree of arteriovenous shunt in tumor bed, and optimizing division of the dose of chemotherapeutic agent when bilateral arterial catheters are used. Quantitative and serial radionuclide angiocardiography has been useful in assessing doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio) toxicity, and 67Ga-citrate imaging has been used to monitor chemotherapy effect on lungs and kidneys. Radionuclide venography can demonstrate suspected thrombus, and the delineation of the vascular anatomy also allows proper placement of another catheter for continuous effective chemotherapy. Serial bone scans have been the primary modality to assess the response of bone metastasis to systemic therapy in breast cancer patients, and nuclear hepatic imaging may show tumor response, hepatocellular dysfunction, and cholecystitis related to chemotherapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)


Arithmetic and brain connectivity: mental calculation in adolescents with periventricular lesions.
The ability for mental calculation represents a fundamental prerequisite for development of intelligence, which is predictive for educational and professional success in life. Many individuals with calculation difficulties are survivors of premature birth. The brain mechanisms of these deficits are, however, largely unknown. In this work, we clarify whether and, if so, how calculation abilities in adolescents who were born premature are related to the extent and topography of periventricular lesions that affect brain connectivity. Performance on a set of mental calculation tasks is lower in adolescents with periventricular leukomalacia (PVL) than in former preterms and term-born peers without signs of brain abnormalities on a magnetic resonance imaging scan. No difference in the calculation ability was found between term-born and preterm adolescents without PVL. Calculation abilities in PVL patients were unrelated to volumetric extent and topography of lesions in both brain hemispheres. Whereas previous work clearly reveals the link between the extent and topography of lesions and severity of impairments in visual cognition ranging from body motion processing to visual navigation and social cognition, no such association occurs for mental calculation. We assume that the lack of relationship between calculation abilities and the extent and topography of periventricular lesions point to topographically restricted neural substrate that serves as the keystone for mental calculation. The findings suggest that periventricular brain damage does not substantially affect the connectivity of this region with other brain structures engaged in the mental calculation network.


Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flufenamic acid, and related compounds have been recently identified as potent inhibitors of AKR1C3. We report that some other NSAIDs (diclofenac and naproxen) also inhibit AKR1C3, with the IC(50) values in the low micromolar range. In order to obtain more information about the structure-activity relationship and to identify new leads, a series of compounds designed on the basis of NSAIDs were synthesized and screened on AKR1C3. The most active compounds were 2-[(2,2-diphenylacetyl)amino]benzoic acid 4 (IC(50)=11microM) and 3-phenoxybenzoic acid 10 (IC(50)=0.68microM). These compounds represent promising starting points for the development of new anticancer agents.


DnaK ATPase activity revisited.
It has recently been reported that the ATPase activity of DnaK, a 70 kDa heat shock protein from E. coli, is autostimulated by increasing protein concentration [(1993) FEBS Lett. 322, 277-279], suggesting that the DnaK dimer may be the enzymatically active species. In this paper we investigated the ATPase activity of different DnaK preparations; we found that the turnover number was very dependent on protein purification. With HPLC-purified DnaK we found a turnover number 20- to 50-fold lower than typical values previously published and no evidence of autostimulation, indicating that the monomer is the active species.


Hormone-responsive alkaline proteinase in rat skeletal muscle is not a mast cell-derived enzyme.
Proteinase activity was determined in myofibrils from intact rat skeletal muscle and from skeletal muscle myocytes grown in culture. In vivo administration of the mast cell degranulator compound 48/80 abolished the alkaline proteinase activity in myofibrils obtained from normal or streptozotocin-diabetic rats. Exposure of myocytes to compound 48/80 in cell cultures had no effect on their myofibrillar proteinase activity, nor did it affect the rate of overall protein degradation in these cells. Co-incubation of cultured mast cells (line P815Y) with myocytes followed by sonication of the cell mixture resulted in a marked reduction of the proteinase activity in the pellet fraction, suggesting that the mast cells contain inhibitor(s) of myofibrillar proteinase activity. It is suggested that the myofibril-bound alkaline proteinase activity is not a mast cell-derived enzyme but a genuine component of muscle cells. The in vivo 48/80-induced reduction of muscle myofibrillar proteinase activity appears to be due to release of a soluble inhibitory activity rather than removal of mast cell proteinase from the tissue by degranulation.


Freeze-fracture electron microscopic observations on the effects of sulphydryl group reagents on human erythrocyte membranes.
Freeze-fracture electron microscopy of human red blood cells at pH 7.4 and 5.5 reveals the presence of membrane elevations (50-100 nm diameter). These are also observed after incubation of the erythrocytes with N-ethylmaleimide but not after incubation with p-chloromercuribenzene sulphonate. Neither of the sulphydryl-group reagents affects the distribution or size of intramembrane particles. The findings are discussed in the light of the effects of mercurials on erythrocyte membrane proteins.


Clinical Presentation of Ocular Surface Squamous Neoplasia in Kenya.
There is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression. To describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability. Prospective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features. Comprehensive history, slitlamp examination, and photography before excision biopsy. Frequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using χ2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the κ statistic. Examiners' assessments were compared with a reference. Among 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P = .002) and tended to have lower levels of education than patients with benign lesions (P = .001). Females predominated (67% of OSSN vs 64% of benign lesions; P = .65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P < .001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P < .001), severe inflammation (6.7% vs 0.3%; P < .001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P < .001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (κ, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%. With overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help.


Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study.
Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients. This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline. A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5-55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P < 0.001). At week 96, virological and biochemical responses were achieved in 34 (94.4%) patients and 20 (76.9%) patients, respectively. Moreover, 21 of 36 (58.3%) patients showed a significant decline in LS value. A higher baseline LS value was a single independent predictor for the reduction in LS value at week 96 from baseline (P < 0.001). During the 144-week TDF therapy, LS values declined significantly in treatment-naïve CHB patients.


Macro-invertebrate populations and production on a salt-marsh in east England dominated by Spartina anglica.
The populations and production of the macroinvertebrates of a Spartina anglica salt-marsh in eastern England were studied over two years. A total of fifteen species were recorded in the sediments, of which twelve species were of regular occurrence, and the total population density recorded ranged from 3,481 m-2 to 11,444m-2 over the twenty-four sampling occasions.The four most abundant species were Nereis diversicolor, Tubifex costatus, Corophium volutator and Hydrobia ulvae. Thirteen further taxa were associated with the canopy of Spartina, with a total population density ranging from 0 to 1,149 m-2. Total monthly standing crop ranged from 1.8 to 8.5 g C m-2 with peaks in July/August in both years. Nereis diversicolor contributed 55% to 86% of total biomass in each month.Production and respiration for each species was determined and annual assimilation calculated. The total annual production was ∼16 g C m-2 a-1 in both 1979 and 1980, with a corresponding assimilation of ∼60 g C m-2 a-1 Nereis diversicolar accounted for >80% of production and assimilation in both years, and the species is clearly of considerable potential importance in the dissipation of Spartina material. The canopy dwelling species accounted for about 1% of the total annual production and assimilation.


Roaring by red deer stags advances the date of oestrus in hinds.
Some male mammals call loudly and repeatedly during the breeding season. Although the song of male birds is known to have effects on male-male competition, mate selection and ovulation, until now the loud calls of male mammals have been shown to affect only competition between males. Although it has been suggested that loud calling could also serve to attract females, the possibility that it has a direct effect on reproduction in females has not previously been investigated for any mammal. Here I report that roaring in red deer (Cervus elaphus) advances ovulation and that harem-holding males can improve their mating success by regular calling.


FGF4 alleviates hyperglycemia in diabetes and obesity conditions.
Increasing evidence suggests that the brain plays a key role in glucose homeostasis, making it a potential target for the treatment of type 2 diabetes (T2D). Sun et al. recently reported that intracerebroventricular (ICV) administration of a single dose of fibroblast growth factor 4 (FGF4) can induce sustained T2D remission in mouse models in the absence of any risk of hypoglycemia.


Prophylactic use of tranexamic acid for decreasing the blood loss in elective cesarean section: A placebo-controlled randomized clinical trial.
Tranexamic acid is used as a known treatment of post-partum hemorrhage both in natural vaginal deliveries and cesarean sections, but its use in elective cesarean as a prophylactic measure to decrease the blood loss is not so common. This clinical trial evaluates the efficacy and safety of tranexamic acid in decreasing the bleeding in women undergoing elective cesarean section. 200 term singleton pregnant women who were scheduled for elective cesarean section were randomized to 2 groups and received a bolus of 1 gm tranexamic acid if body weight was <90 kg and 1.5 g if body weight was >90 kg diluted in 15 ml of 5% dextrose intravenously, or 5 ml of distilled water in 15 ml of 5% dextrose as placebo (before skin incision). Intra-operative and post-operative blood loss and hemoglobin levels were compared. Tranexamic acid decreased the mean blood loss by 25.3 % in our studied women. Mean volume of intra-operative blood loss was 391.1 (±67.4) ml in tranexamic acid group and 523.8 (±153.4) ml in control group which was statistically significant lesser with a 132.7 ml difference. Rate of >1000 ml and >500 ml bleeding and need to blood transfusion were also statistically significant lower in tranexamic acid group., mean hemoglobin level was statistically significant lower in placebo group than tranexamic acid group (11.77 ± 0.50 versus 11.31 ± 0.56) 6 h after cesarean section. No adverse reaction was documented. Prophylactic use of intravenous tranexamic acid decreases the blood loss safely in women undergoing elective cesarean section.


Generating fast-twitch myotubes in vitro with an optogenetic-based, quantitative contractility assay.
The composition of fiber types within skeletal muscle impacts the tissue's physiological characteristics and susceptibility to disease and ageing. In vitro systems should therefore account for fiber-type composition when modelling muscle conditions. To induce fiber specification in vitro, we designed a quantitative contractility assay based on optogenetics and particle image velocimetry. We submitted cultured myotubes to long-term intermittent light-stimulation patterns and characterized their structural and functional adaptations. After several days of in vitro exercise, myotubes contract faster and are more resistant to fatigue. The enhanced contractile functionality was accompanied by advanced maturation such as increased width and up-regulation of neuron receptor genes. We observed an up-regulation in the expression of fast myosin heavy-chain isoforms, which induced a shift towards a fast-twitch phenotype. This long-term in vitro exercise strategy can be used to study fiber specification and refine muscle disease modelling.


Less power or powerless? Egocentric empathy gaps and the irony of having little versus no power in social decision making.
The authors investigate the effect of power differences and associated expectations in social decision making. Using a modified ultimatum game, the authors show that allocators lower their offers to recipients when the power difference shifts in favor of the allocator. Remarkably, however, when recipients are completely powerless, offers increase. This effect is mediated by a change in framing of the situation: When the opponent is without power, feelings of social responsibility are evoked. On the recipient side, the authors show that recipients do not anticipate these higher outcomes resulting from powerlessness. They prefer more power over less, expecting higher outcomes when they are more powerful, especially when less power entails powerlessness. Results are discussed in relation to empathy gaps and social responsibility.


Psychological Difficulties in Children and Adolescents during the COVID-19 Lockdown: The Effects of Spending Free Time with Parents or Using Digital Devices.
The present study investigated protective and risk factors for psychological difficulties in children and adolescents during the COVID-19 lockdown. Specifically, the role of increased use of digital devices (DDs) for recreational purposes and the role of free time spent with parents were explored. Furthermore, the possible mediating effect of increased use of DDs in the relationship between free time spent with parents and psychological difficulties was tested. Participants were 4412 Italian children and adolescents, divided into two groups: children aged 6-10 years (n = 2248) and adolescents aged 11-18 years (n = 2164). Data were collected in Italy during the national lockdown and questionnaires were completed online by parents, who reported on their children's habits. The daily use of DDs increased significantly during the lockdown compared to the previous period, in both children and adolescents. Additionally, psychological difficulties increased in both children and adolescents during the lockdown, with a more severe impairment for children. Increased use of DDs during the lockdown positively predicted psychological difficulties (children: beta = 0.18, p < 0.001; adolescents: beta = 0.13, p < 0.001), while free time spent with parents was protective (children: beta = -13, p < 0.001; adolescents: beta = -0.12, p < 0.001). For children (but not adolescents), increased use of DDs mediated the effects of free time spent with parents on psychological difficulties (children: beta = -0.01, 95% CI [-0.018, -0.002]; adolescents: beta = -0.003, 95% CI [-0.009, 0.003]). The findings provide new insights for education and research.


Validation of Multi-epitope Peptides Encapsulated in PLGA Nanoparticles Against Influenza A Virus.
Influenza is a highly contagious respiratory disease which poses a serious threat to public health globally, causing severe diseases in 3-5 million humans and resulting in 650,000 deaths annually. The current licensed seasonal influenza vaccines lacked cross-reactivity against novel emerging influenza strains as they conferred limited neutralising capabilities. To address the issue, we designed a multi-epitope peptide-based vaccine delivered by the self-adjuvanting PLGA nanoparticles against influenza infections. A total of six conserved peptides representing B- and T-cell epitopes of Influenza A were identified and they were formulated in either incomplete Freund's adjuvant containing CpG ODN 1826 or being encapsulated in PLGA nanoparticles for the evaluation of immunogenicity in BALB/c mice. The self-adjuvanting PLGA nanoparticles encapsulating the six conserved peptides were capable of eliciting the highest levels of IgG and IFN- γ producing cells. In addition, the immunogenicity of the six peptides encapsulated in PLGA nanoparticles showed greater humoral and cellular mediated immune responses elicited by the mixture of six naked peptides formulated in incomplete Freund's adjuvant containing CpG ODN 1826 in the immunized mice. Peptide 3 from the mixture of six peptides was found to exert necrotic effect on CD3+ T-cells and this finding indicated that peptide 3 should be removed from the nanovaccine formulation. The study demonstrated the self-adjuvanting properties of the PLGA nanoparticles as a delivery system without the need for incorporation of toxic and costly conventional adjuvants in multi-epitope peptide-based vaccines.


A survey on patients' knowledge and expectations during informed consent for spinal surgery: can we improve the shared decision-making process?
The informed medical consent in surgery requires to some point basic medical knowledge. The treating physicians while explaining the details and risks of the recommended procedure often imply this. We hypothesized, that patients do not have adequate medical understanding to decide about the ongoing therapy and its potential complications based on knowledge jeopardizing the patients' safety. We conducted a retrospective analysis of a prospective database using a multiple choice questionnaire with 10 basic questions about anatomy, clinical symptoms and therapies of spinal diseases in our spine clinic at a German university hospital. Included were all patients at the spine clinic who agreed to the study and to fill in the questionnaire. Furthermore the patients age, mother tongue, the past spinal surgical history, the length of duration of symptoms and the patients education were inquired. The data were analyzed descriptive. Included were 248 patients with an average age of 59 years (16-88 a). 70 % of all patients used German as their mother tongue. 30 % of the included patients already had spinal surgery and suffered on average for 13.4 years because of their spinal disorder. Overall 32.6 % of all questions were answered correctly (range 0.8-68 %). A correlation of correctly answered questions and the patients' age, duration of symptoms, mother tongue, education and past surgical history could not be described. The percentage of correctly answered questions is almost as low as the likelihood of nearness in guessing. Having this in mind the patients do not choose any treatment option based on knowledge. The physicians need to provide more basic knowledge to the patients. This would increase the amount of successful therapies, content patients and the patients safety.


Health care access and support for disabled women in Canada: falling short of the UN Convention on the Rights of Persons with Disabilities: a qualitative study.
The United Nations Convention on the Rights of Persons with Disabilities and other international human rights conventions guarantee the fundamental human rights to physical, social, and psychological health. The purpose of this study was to examine whether these rights are being upheld in Canada for disabled women. An interpretive, qualitative, focus group design was employed. Participants were women 18 to 67 years of age with a self-identified physical, sensory, cognitive, and/or psychiatric impairment. Eleven focus groups were conducted with 74 disabled women from urban and rural settings in Northern Ontario, Manitoba, and Nova Scotia. The data were analyzed for themes using a flexible coding system derived from and consistent with the research objectives and the study's human rights framework. Participants described multiple intersecting factors that impeded or facilitated access to health care. Services included both generic health services and impairment-specific services. Participants experienced a number of barriers accessing professionals, support programs, and services. These are described under three broad themes: 1) Labyrinthine health service 'systems,' 2) assumptions, attitudes, and discriminatory practices, and 3) inadequate sexual health or reproductive services and supports. The results suggest that Canada falls significantly short of guaranteeing disabled women's human rights to access health care supports and services. Access barriers resulted from the inefficiencies and complexities of the multiple agencies and programs that disabled women had to navigate, difficulties accessing information on available services, and negative attitudes of some health and social service providers.


Temperament and character profile of patients with psoriasis.
Psychosocial factors have been implicated as being important in the onset and/or exacerbation of psoriasis.(1) The aim of this study is to examine both the personality factors of patients with psoriasis and the correlations between temperament and character dimensions. A total number of 105 psoriasis patients and 109 healthy individuals were enrolled in the study. Questionnaires including Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Temperament and Character Inventory (TCI) were administered individually. Both groups were evaluated in terms of depression, anxiety and characteristic features by using these psychological tests and compared statistically. The relationship between psoriasis area and severity index (PASI) score and the BDI, BAI and TCI scales were also evaluated. The mean BDI score of the psoriasis group were significantly higher than the control group. The psoriasis group had significantly higher scores of harm avoidance and lower scores of being self-directedness than the control group. The duration of psoriasis and the PASI scores were not correlated with BDI and BAI scores. The current study shows that psoriasis patients have distinctive temperament and character dimensions when compared with the control group. We suggest that evaluation and treatment of psoriasis should also include psychosomatic approaches in clinical practice.


A comparison of the effectiveness of three neck-hold killing traps in occluding carotid arteries in the neck of the brushtail possum.
To compare the potential humaneness of three types of neck-hold killing traps in terms of the blood vessels that are occluded, and to examine the anatomy of the blood vessels that supply blood to the possum's brain. The prevalence of occlusion of the common carotid arteries and the trachea was examined in 33 possums which were caught with Timms, LDL and Conibear 160 traps. The anatomy of the blood supply to the brain was examined in six possums using a resin casting technique. The prevalence of complete bilateral common carotid artery occlusion was 77% for the Timms trap, 45% for the LDL trap and 22% for the Conibear 160 trap. The major route for blood supply to the brain was via the common carotid arteries. Where the aim is to kill possums quickly by ischaemia of the brain, the Timms trap is to be preferred over the LDL and Conibear 160 traps.


Investigation of tumor suppressor genes apart from VHL on 3p by deletion mapping in sporadic clear cell renal cell carcinoma (cRCC).
To investigate the most recurrent deletion loci on 3p12-p26 by deletion mapping studies by PCR-LOH and BAC array-FISH in sporadic conventional renal cell carcinoma (cRCC) and further, to evaluate the their clinicopathologic significance in cRCC. Comparative allelotyping studies in cRCC and major epithelial carcinomas (MEC) such as lung, breast, and bladder tumors were also carried out to investigate the specificity of the targeted loci in cRCC. A total of 40 c-RCC patients were enrolled in this study, categorized in to 2 groups: group I comprises of patients of stages I and II and group II includes patients at stages III and IV. Loss of heterozygosity (LOH) studies were performed by PCR using 15 microsatellite markers of region 3p12-p26 on paired normal-tumor tissues. The recurrent LOH loci found in 27 cRCC tumors were further validated by BAC array-FISH using 23 serially mapped BAC clones. Simultaneously, the allelic deletion status of fragile histidine triad (FHIT) gene was studied by FISH in cRCC and major epithelial carcinoma (MEC) tumors. The numerical aberrations of chromosome 3 were also studied using the centromere enumeration probe (CEP) probe for chromosome 3 to validate the observed allelic losses by BAC array-FISH in cRCC as well as MECs. Our study revealed 3 affected regions of LOH on 3p in cRCC: 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 in both group I (stages I and II) and group II (stage III and IV). Comparative allelotyping studies revealed that except for LOH loci D3S2406 (20%), D3S1766 (14%), and D3S1560 (20%), remaining affected loci revealed retention of heterozygosity (ROH) in breast carcinomas. Lung and bladder tumors revealed ROH at all affected LOH loci. FISH with FHIT gene probe revealed deletions in cRCC (88%), breast (30%), and lung tumors (10%). FHIT gene deletions frequency was almost equal in both groups I and II (>70%), whereas a locus 3p13 (D3S2454) revealed the highest LOH in group II (83%) patients in comparison to group I (16%). BAC array-FISH studies in cRCC identified 15 recurrent deletion loci at crucial regions, 3p12.2, 3p14.2, 3p21.3, and 3p24.2-p26 with long continuous deletion of 3p14.1-p26.1 exclusively in patients of stages III and IV. Validation of LOH loci in breast carcinomas by BAC array-FISH with BAC clones mapped at these loci revealed comparatively lower deletion frequency for RP11-59E22 (3p12.2) (30%), RP11-759B7(3p21.1) (12%), and RP11-57D6 (3p25.2, proximal to VHL) (15%) than cRCC. Molecular cytogenetic studies by BAC array-FISH was found to be more sensitive over LOH. Deletion patterns on 3p explored that deletion of FHIT and flanking loci may occur as an initiating event followed by deletions at 3p12.2, 3p21.31-3p21.32, and 3p24.2-3p26.1 in the initial stage of development of disease, while continuous large deletions of 3p21.3-3p26.1 and 3p14.1-3p26.1 occur as progressive deletion due to genetic instability. Lack of VHL along with flanking loci in 50% cRCC patients that included both groups I and II supported the hypothesis of both VHL dependent and VHL independent pathways in cRCC tumorigenesis. Comparative allelotyping studies in cRCC and MECs indicated association of specific targeted loci including VHL in cRCC. Further expansion of these studies with characterization of the genes at targeted loci and correlation with clinical outcome will explore the prognostic significance and also provide an insight into the mechanisms of tumor suppressive pathways in genitourinary cancers such as CRCC.


Endoscopic Management of Fourth Ventricle Neurocysticercosis: Description of the New Technique in a Case Series of 5 Cases and Review of the Literature.
Around 7%-33% of cases of neurocysticercosis (NCC) have intraventricular involvement, and the fourth ventricle is the most frequent site. Medical management and various surgical approaches have been described for treating this disease. The objective of this study was to describe technical modification for endoscopic fourth ventricular NCC removal in a series of 5 cases. In this study (January 1, 2016, to December 31, 2017), all cases of fourth ventricular NCC which were treated with a special technique (endoscopic transcortical transforaminal transaqueductal approach) using a rigid endoscope system and 6-French infant feeding tube (IFT) were included in the study. The IFT was passed through the main channel, the cyst was engaged at the tip by applying gentle suction with a 20 cm3 syringe, and the cyst was removed along with the whole endoscopic assembly. Patient's clinical, radiologic, and follow-up data were retrieved from the department database records. Five patients (3 men, 2 women; mean age, 20 years; range, 11-27 years) were enrolled. All patients had features of raised intracranial pressure. Two patients also had drop attacks, and one presented with altered sensorium and one had upgaze palsy. Duration of symptoms ranged from 3 months to 3 years. All patients had isolated fourth ventricular NCC with obstructive hydrocephalus. Complete removal of the neurocysticercal cyst could be performed in all patients without any injury to the periaqueductal region or fornix. There was no intraoperative rupture of the neurocysticercal cyst. On follow-up (range, 12-28 months; mean, 19.4 months), all patients had relief of symptoms and imaging showed no cyst and hydrocephalus. We conclude that our endoscopic approach is safe, simple, cost-effective, and allows minimally invasive removal of the fourth ventricle cyst and treatment of hydrocephalus without any morbidity.


Human gut-microbiome-derived propionate coordinates proteasomal degradation via HECTD2 upregulation to target EHMT2 in colorectal cancer.
The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.


Methods to teach schoolchildren how to perform and retain cardiopulmonary resuscitation (CPR) skills: A systematic review and meta-analysis.
Worldwide, bystander CPR rates are low; one effective way to increase these rates is to train schoolchildren; however, the most effective way to train them is currently unknown. This systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, evaluated whether CPR training for schoolchildren, using innovative teaching modalities (nonpractical, self, or peer-training) versus standard instructor-led training, resulted in higher quality CPR, self-confidence and short-term (≤3 months post-training) or long-term (>3 months post-training) retention of CPR skills. From 9793 citations, 96 studies published between 1975 and 2022 (44 RCTs and 52 before/after studies) were included. There were 43,754 students, average age of 11.5 ± 0.9 (range 5.9-17.6) and 49.2% male. Only 13 RCTs compared practical vs. nonpractical training (n = 5), self- vs. instructor-led training (n = 7) or peer- vs. instructor-led training (n = 5). The observed statistically significant differences in mean depth and rate of compressions between children with hands-on practical training and those without were not clinically relevant. Regardless of training modality, compression depth was consistently suboptimal. No differences were observed in CPR skills immediately or ≤ 3 months post-training, between children who were self- or peer-trained vs. instructor-led. Due to lack of data, we were unable to evaluate the impact of these novel training modalities on student self-confidence. Although innovative training modalities are equally effective to instructor-led training when teaching schoolchildren CPR, compression depth was frequently suboptimal. Recommendations on standardized training and evaluation methods are necessary to understand the best ways to train children.


An unknown world in the Neotropical region: a complete life cycle of a new species of Monoclona Mik, 1886 (Diptera: Mycetophilidae: Sciophilinae).
Popularly known as fungus gnats, Mycetophilidae are found in humid environments usually associated with mushrooms and decaying wood. Their immature forms often feed on fungus fruiting bodies. Similar to most bibionomorphans, mycetophilids need due attention concerning their taxonomy and information on their natural history, especially in the Neotropical region. This work describes Monoclona carambeiensis sp. nov., a new species of Monoclona Mik, and furnishes information on the morphology of adults and immatures, besides notes and photographs on the life cycle of the species. Immature forms present on a piece of decaying wood with lichens and fungi were collected from Carambe, Paran, and reared in the laboratory. The emerged adult male was fixed in 80% ethanol. This is the first study describing an immature of a Neotropical species of Monoclona, and also the first record of the genus in the state of Paran, Brazil. This is the third Neotropical species of Mycetophilidae to have its life cycle described, for a fauna with over 1,100 known species.


Temporal air quality (NO2, O3, and PM10) changes in urban and rural stations in Catalonia during COVID-19 lockdown: an association with human mobility and satellite data.
In this study, changes in air quality by NO2, O3, and PM10 in Barcelona metropolitan area and other parts of Catalonia during the COVID-19 lockdown with respect to pre-lockdown and to previous years (2018 and 2019) were evaluated. Selected air monitoring stations included 3 urban (Gràcia, Vall d'Hebron, and Granollers), 1 control site (Fabra Observatory), 1 semi-urban (Manlleu), and 3 rural (Begur, Bellver de Cerdanya, and Juneda). NO2 lockdown levels showed a diminution, which in relative terms was maximum in two rural stations (Bellver de Cerdanya, - 63% and Begur, - 61%), presumably due to lower emissions from the ceasing hotel and ski resort activities during eastern holidays. In absolute terms and from an epidemiologic perspective, decrease in NO2, also reinforced by the high amount of rainfall registered in April 2020, was more relevant in the urban stations around Barcelona. O3 levels increased in the transited urban stations (Gràcia, + 42%, and Granollers, + 64%) due to the lower titration effect by NOx. PM10 lockdown levels decreased, mostly in Gràcia, Vall d'Hebron, and Granollers (- 35, - 39%, and - 39%, respectively) due to traffic depletion (- 90% in Barcelona's transport). Correlation among mobility index in Barcelona (- 100% in retail and recreation) and contamination was positive for NO2 and PM10 and negative for O3 (P < 0.001). Satellite images evidenced two hotspots of NO2 in Spain (Madrid and Barcelona) in April 2018 and 2019 that disappeared in 2020. Overall, the benefits of lockdown on air quality in Catalonia were evidenced with NO2, O3 and PM10 levels below WHOAQG values in most of stations opposed to the excess registered in previous years.


Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates.
Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m-2) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg (P < 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time (P = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, P = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, P < 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.


Maternal depressive symptoms during and after pregnancy are associated with poorer sleep quantity and quality and sleep disorders in 3.5-year-old offspring.
Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks + days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child's mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory-II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics.


The effects of chemical injury on the ocular surface.
Chemical burns of the eye may destroy all of the corneal epithelium and large portions of conjunctival epithelium into the fornices. Restoration of the ocular surface after a chemical burn depends on the centritedal movement of conjunctival epithelial cells and their adherence to the altered corneal stroma. Epithelial movement after a corneal burn is normal for 72 hours after a burn, but persistent epithelial defects thereafter commonly are not resolved until total corneal vascularization occurs. Although this fresh epithelium may be protected by a bandage soft contact lens, more promising and far-reaching approaches may follow epithelial supplementation and even replacement. The link between the health and integrity of the epithelial layer as it relates to the corneal substratum and its cellular constituents remains to be forged.


Interpretive criteria for temocillin disk diffusion susceptibility testing.
The susceptibility of 677 clinical bacterial isolates to temocillin was determined by broth microdilution and disk diffusion methods for the purpose of evaluating disks with three different temocillin concentrations and determining the temocillin disk diffusion interpretive criteria. The 60 microgram temocillin disk provided the highest interpretive accuracy (96.2%), although the 30 microgram disk differed by having only three (1.2%) additional minor interpretive errors. Based on available temocillin pharmacokinetics and recommended dosage schedules, the minimum inhibitory concentration breakpoints chosen were: greater than or equal to 32 micrograms/ml = resistant and less than or equal to 16 micrograms/ml = susceptible. The corresponding disk diffusion zone diameter breakpoints for the 60 microgram disk were less than or equal to 17 mm and greater than or equal to 21 mm; zone diameters of 18-20 mm were considered intermediate. For the 30 microgram disk these were less than or equal to 15 mm, greater than or equal to 19 mm and 16-18 mm respectively.


Effect of stressors on family adaptation in stroke patients: A parallel multivariable mediation model.
The mechanisms underlying how stressors affect family adaptation are unclear. This study determined the relationship between stressors and family adaptation among stroke patients, particularly the parallel mediating role of family function and family resilience. The study was conducted in the neurology ward of a tertiary hospital in China. A total of 335 stroke inpatients were interviewed face-to-face from August 2020 to March 2021. A questionnaire was administered that included demographic characteristics, the Family Inventory of Life Events and Changes, Family Apgar Index Scale, Family Hardiness Index Scale, and Family Adaptation Scale. The demographic data and correlations among the research variables were analyzed. A bootstrap method using the SPSS PROCESS macro was employed to test a mediation model. Family adaptation was negatively related to stressors (r = -0.291, p < 0.01) and positively related to family function (r = 0.531, p < 0.01) and family resilience (r = 0.393, p < 0.01). Furthermore, family function and family resilience played parallel mediating roles between stressors and family adaptation. This study elaborated how stressors interacted with family adaptation through the mediation of family function and family resilience. The findings suggest that enhancement of family function and family resilience may help to improve family adaptation among stroke patients.


A Thiophene-2-carboxamide-Functionalized Zr(IV) Organic Framework as a Prolific and Recyclable Heterogeneous Catalyst for Regioselective Ring Opening of Epoxides.
A new thiophene-2-carboxamide-functionalized Zr-UiO-66 MOF (1) was synthesized by employing a traditional solvothermal procedure. Compound 1 displayed high thermal (up to 340 °C under an Ar atmosphere) and chemical stability (in water, 1 M HCl, and acetic acid). A nitrogen physisorption measurement with the activated form of 1 (denoted 1') exhibited a BET surface area (781 m2/g) despite attachment of a bulky side chain with the linker molecule. Compound 1' was able to heterogeneously catalyze the ring-opening reaction of epoxides with amines. Catalyst 1' exhibited significant yields as well as wide substrate scope in the ring opening of epoxides by means of amines. It also displayed better catalytic performance in comparison to known MOF catalysts such as Cu3(BTC)2, Fe(BTC) (BTC: 1, 3, 5-benzenetricarboxylate), and Zr-UiO-66. Control experiments were performed with free linker, Zr(IV) salt and without catalyst 1', confirming the exclusive role of 1' in the catalytic reaction. The reusability characteristics of catalyst 1' was established for up to five consecutive catalytic cycles. The synthesis and characterization of the linker molecule, material 1, and 1' and mechanism of the catalysis reaction were studied elaborately.


Parkinson's Disease and Its Management: Part 4: Treatment of Motor Complications.
Parkinson's motor complications include wearing-off, a delayed or absent response to carbidopa/levodopa therapy, freezing of gait, dyskinesias, and dystonias. Treatment may include medication adjustments, such as increased dopaminergic stimulation.


Enhancing urban ecological resilience through integrated green technology progress: evidence from Chinese cities.
The effective resolution of environmental pollution caused by carbon haze through coordinated progress in green technology and urban ecological resilience is a crucial approach towards promoting sustainable development in Chinese cities. In this study, panel data from 281 cities in China from 2007 to 2019 were analyzed using the entropy method and the coupling coordination degree model to determine the coupling coordination degree between green technology progress and urban ecological resilience. The coordinated influence model and threshold model were applied to investigate coupled coordination types and influencing factors. Results indicate that green technology progress levels have shown an upward trend with increasing volatility from east to west and decreasing volatility with urban scale expansion. Ecological resilience levels have also steadily increased, albeit at a reduced rate. The coupling coordination degree of green technology progress and urban ecological resilience has evolved overall from low to high levels; however, the coupling coordination type has regressed to some extent, with most regions exhibiting lagging green technological progress. Pressure resilience has a positive impact on the coupling coordination degree, while state resilience and response resilience have a negative impact. Green technology progress has a dual threshold effect on the coupling coordination degree. By exploring the coupling and coordination mechanism between green technology progress and urban ecological resilience, this study not only facilitates collaborative management of pollutants and greenhouse gases in cities but also provides a comprehensive reference for the construction of an institutional system for collaborative carbon and haze management.


Translation machinery: the basis of translational control.
Messenger RNA (mRNA) translation consists of initiation, elongation, termination, and ribosome recycling, carried out by the translation machinery, primarily including tRNAs, ribosomes, and translation factors (TrFs). Translational regulators transduce signals of growth and development, as well as biotic and abiotic stresses, to the translation machinery, where global or selective translational control occurs to modulate mRNA translation efficiency (TrE). As the basis of translational control, the translation machinery directly determines the quality and quantity of newly synthesized peptides and, ultimately, the cellular adaption. Thus, regulating the availability of diverse machinery components is reviewed as the central strategy of translational control. We provide classical signaling pathways (e.g., integrated stress responses) and cellular behaviors (e.g., liquid-liquid phase separation) to exemplify this strategy within different physiological contexts, particularly during host-microbe interactions. With new technologies developed, further understanding this strategy will speed up translational medicine and translational agriculture.


Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus.
Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 μg/μl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria.