Assortative mating and directional or stabilizing selection for a non-linear function of traits in Tribolium.
Assortative or random mating following selection in either direction on a non-linear index (experiment 1) or stabilizing selection for pupal length (experiment 2) were carried out for five generations in two lines of Tribolium castaneum (A and R, respectively), with three replicates each. The selected proportion was 25% in all lines. In experiment 1, the selection criterion was designed to increase the aggregate value of adult weight and the first- and second-order powers of pupal length. The A and R lines gave significant responses for the aggregate value (184 ± 6 and 161 ± 14, respectively), pupal length (0.74 ± 0.02 and 0.64 ± 0.05, respectively), and adult weight (0.79 ± 0.03 and 0.78 ± 0.12, respectively). Although the A line was not significantly better than the R line, there was a consistent advantage for assortative mating over random mating, the mean response for aggregate value and pupal length being approximately 1.15 times greater for the A line. In experiment 2 the selection criterion was the square of the deviation from the mean pupal length (stabilizing selection); both lines did not show any change for pupal length. The phenotypic variance showed a significant decrease in the A and R lines, due to a decrease in between-family variance. The assortatively and randomly mated lines were similar for these changes in phenotypic variation. RESUMEN: Aparemiento clasificado y selección direccional o estabilizante para una función no lineal en Tribolium. Dos líneas de Tribolium castaneum fueron seleccionadas direccionalmente para un índice no lineal (experimento 1) o estabilizantemente para longitud de pupa (experimento 2), apareando los animales seleccionados clasificadamente (A) o aleatoriamente (R). Había tres repeticiones por experimento y línea, siendo la proporción de selección el 25%. En el experimento 1, el objetivo de selección incluía el peso adulto así como la longitud de pupa y su cuadrado. Ambas líneas dieron respuesta significativa para el valor agregado y sus dos caracteres componentes. Había una ventaja consistente aunque no significativa para el apareamiento clasificado, siendo la respuesta media para valor agregado y longitud de pupa 1.15 veces mayor en la línea A. En el experimento 2, el criterio de selección era el cuadrado de la desviación con respecto a la media de longitud de pupa (selección estabilizante); ambas líneas no mostraron ningún cambio significativo en longitud de pupa. La varianza fenotípica tuvo una disminución significativa debida a una reducción de la varianza genética, siendo estos cambios similares en ambas líneas. ZUSAMMENFASSUNG: Assortative Paarung, gerichtete oder stabilisierende Selektion für nicht-lineare Funktion von Merkmalen in Triboleum Assortative oder Zufallspaarung nach gerichteter Selektion in beiden Richtungen für nicht-lineare Merkmale (Versuch 1) oder stabilisierende für Puppenlänge (Versuch 2) wurden über 5 Generationen bei Triboleum castaneum (A bzw. R), mit je 3 Wiederholungen und 25% Remonte, durchgeführt. In Versuch 1 sollten adultes Gewicht und 1. und 2. Potenz der Puppenlänge gesteigert werden. A und R Linien ergaben signifikante Selektionserfolge für Gesamtwert (184 ± 6 bezw. 161 ± 14), Puppenlänge (0,74 ± 02, 0.64 ± 05) und adultes Gewicht (0.74 ± 03 und 0.78 ± 0.12). Obwohl Linie A nicht statistisch signifikant überlegen war, zeigte sich durchgehend überlegenheit gegenüber R Linien, im Durchschnitt 1,15 mal. In Versuch 2 zeigte keine der beiden Linien Veränderungen der Puppenlänge, aber die Varianz nahm signifikant ab wegen Verminderung der Varianz zwischen Familien, deren Abnahme in der zufalls- und in der assortativ gepaarten Linie gleich groß war. RÉSUMÉ: Accouplement classé et sélection directionelle o stabilisant pour une fonction no lineal chez Tribolium Deux lingnées de Tribolium castaneum on été soumis a sélection directionelle par un index no lineal (Expérience 1) o stabilisant pour la longeur de la pupae (Expérience 2), avec accouplement des animaux sélectiones de façon classé (A) ou aléatoire (R). Le travail compris 3 répétitions pour chacune des expériences et lignée, avec une presion de sélection du 25%. Dans l'expérience 1 l'objetive de sélection était composé pour le poids adult, la longeur de la pupae et sa carrée. On a obtenû une réponse significative chez les deux lignées por l'agregé et aussi pour les deux caractéres. On a obtenû une superiorité no significative mais consistant de l'accouplement classé, étant la réponse moyenne pour l'agregé et la longeur de la pupae 1.15 fois plus grand chez la lignée A. Pour l'experience 2 le critére de selection etait le carrée de la deviation a la moyenne de la longeur de la pupae (sélection stabilisant); aucune des lignees montrait changes significatives pour la longeur de la pupae. La variation phénotypique montre une réduction significative ` cause de la réduction du variation génétique, avec changes similaires chez les deux lignees.


Total laparoscopic pelvic exenteration for a laterally recurrent cervical carcinoma with a vesicovaginal fistula that developed after concurrent chemoradiotherapy.
For locally advanced cervical carcinoma, concurrent chemoradiotherapy (CCRT) is the standard treatment, however, CCRT can lead to development of a vesicovaginal or rectovaginal fistula [1]. Treatment options are limited for patients with laterally recurrent cervical carcinoma and fistula formation after CCRT. Chemotherapy with bevacizumab is now used for recurrent or advanced cervical carcinoma, but this treatment is associated with fistula formation [2]. When the recurrent mass is confined to the pelvic cavity, complete surgical resection with negative margins offers the most promise; however, the resectability rate is low in cases of laterally recurrent tumor [3], which may include bony structures, and survival outcomes seem to be poor in cases of a laterally recurrent vs. centrally recurrent tumor, even when the primary tumor has been resected in full [4]. Because analyses have shown that laparoscopy optimizes visualization and thus provides for meticulous dissection and that laparoscopic pelvic exenteration, in comparison to open pelvic exenteration results in minimal intraoperative blood loss and complications, fewer postoperative complications, and a shorter hospital stay [5], we perform laparoscopic pelvic exenteration in cases of laterally recurrent cervical carcinoma. A 52-year-old woman underwent CCRT for a 10-cm stage IVA cervical carcinoma. That involved the bladder and right ureter, causing right hydronephrosis. Seven months after the CCRT, a recurrent mass at the right pelvic sidewall and vesicovaginal fistula were detected. The mass involved the right ureter and bladder and was attached to the rectum. The patient's right renal function was lost. Total pelvic exenteration and right nephroureterectomy were performed laparoscopically. Operation time was 566min, and the blood loss volume was 250mL. Complete tumor clearance was achieved without any complication. No adjuvant treatment has been performed, and follow-up positron emission tomography-computed tomography has revealed no sign of recurrence during the 5months that have passed since the surgery. Total laparoscopic pelvic exenteration is technically feasible for a laterally recurrent cervical carcinoma and vesicovaginal fistula that develop after CCRT.


Possible evidence of near transfer effects after adaptive working memory training in persons with multiple sclerosis.
Cognitive deficits, especially in working memory (WM) and information processing (IP) efficiency, are common in people with multiple sclerosis (PwMS). Few studies have examined the efficacy of n-back training in improving these two cognitive functions in PwMS. In the present study, we examined the effects of an intensive n-back training program by measuring the gains on the trained task (2- and 3-back tasks), but we also studied possible near transfer effects to other tests that assess WM and IP, as well as far transfer effects or improvements in other cognitive functions. A sample consisting of 35 PwMS with different cognitive statuses. All the participants underwent an adaptive n-back training for 10 days (60 min/day), and they were neuropsychologically assessed at baseline (D1) and after training (D10). The effectiveness of the training was tested: (1) by using mean-based comparisons and Cohen's d values; (2) by estimating and comparing the quartile values of the D1 and D10 distributions. Two indexes of improvement in individual performance were calculated, the net score improvement index (NSI) and the percent of maximum possible individualized improvement (PMPI). Repeat practice improves 2- and 3-back performance, showing more correct responses (CR) and lower reaction times (RT) on D10 compared to D1. These results were corroborated by the NSI and PMPI scores, but the gains after training were more statistically significant for the 3-back (observing higher CR and lower RT after training) than for the 2-back (observing gains in CR, but not in RT). We also observed a possible transference of this improvement on the n-back task to other WM/IPS tests. Specifically, statistically significant pre-post training differences were found in the values in three quartiles of the Paced Auditory Serial Addition Test (PASAT; q25, p < 0.03; q50, p < 0.001; q75, p < 0.002) and of the Symbol Digit Modalities Test (SDMT; q25, p < 0.03; q50, p < 0.001; q75, p < 0.001) as well as in two quartiles of the Letter-Number Sequencing Task (LNST; q50, p < 0.004; q75 p < 0.001), and in one quartile of the Digit Backwards Span Test (DSBT; q75, p < 0.001). Reliable change analyses confirmed these performance improvements on the PASAT, SDMT, and LNST. This study confirmed that the intensive and adaptive n-back training produced improvements in the trained task in PwMS with different cognitive statuses. Furthermore, these gains were not only observed on the trained task, but they seemed to be also transferred to other tests that measured WM and IP functions.


Netrin-1 overexpression is predictive of ovarian malignancies.
Netrin-1 (NTN1) is functionally important for the development of the nervous system.Interestingly, few recent studies showed that NTN1 may also promote cancer by increasing survival and resistance of lung and breast cancer cells to apoptosis. Our purpose was to investigate whether NTN1 and its receptor DCC may be involved in ovarian cancer. The NTN1 and DCC mRNAs were quantified by real-time RTPCR in normal (10), benign (8) and cancer (17) ovarian tissues. ALAS1 and TBP housekeeping genes were used for normalization. NTN1 was found overexpressed in 76% of ovarian cancer specimens (13/17) as compared to normal (0/10, p<0.004)and benign (1/8, p<0.008) samples. Increased NTN1 mRNA levels correlated with advanced tumor stage (stage III, n=8, 100%) and grade (grade 3, n=7, 100%). In contrast, DCC was found downregulated in 59% (10/17) of ovarian tumors tested but correlation was not significant when compared to normal or benign specimens. Here,we demonstrated that NTN1 may be involved in ovarian cancer as the expression of NTN1 mRNA is strongly upregulated in ovarian malignant tumors but not in benign tumors. The fact that increased NTN1 is specifically observed in cancerous tissues indicates that NTN1 may represent a novel candidate biomarker for ovarian cancer.


Acquired von Willebrand syndrome in monoclonal gammopathy - A scoping review on hemostatic management.
Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management. We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS-MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted. To describe the clinical presentation and outcomes of different therapeutic approaches. Seventy-five studies were included in the final review, for a total of 137 patients. Most patients had von Willebrand factor ristocetin cofactor activity <30 IU/dL (86.6%) and factor VIII levels <50 IU/dL (91.8%). Bleeding severity ranged from no bleeding (16.1%) to minor bleeding (46.4%) and major bleeding (37.5%). The overall clinical success rates for 1-deamino-8-D-arginine vasopressin (DDAVP), factor replacement therapy, and intravenous immunoglobulin (IVIG) were 43.8%, 33.3%, and 85.4%, respectively. The laboratory response rates for DDAVP, factor replacement therapy, and IVIG were 39.0%, 62.9%, and 88.6%, respectively. Several other treatments were also reported in small numbers, out of which myeloma-directed therapies, plasma exchange, recombinant factor VIIa, and antifibrinolytics appeared most successful, while immunosuppressive agents were largely ineffective. IVIG appears to be an effective treatment for AVWS-MGUS bleeding, conferring a high clinical success rate with measurable laboratory outcomes; albeit temporary. DDAVP and factor replacement therapy may be partially successful in controlling minor bleeds, but not major bleeds. Other less commonly used agents may be effective in certain cases, although data are limited.


Effects of inlet velocity and structure parameters on the performance of a rotary diesel particulate filter for truck diesel engine based on fuzzy grey relational analysis.
In this paper, a three-dimensional mathematical model of the rotary diesel particulate filter (RDPF) for truck diesel engine is established according to the fluid mechanics and porous media theory. The effects of inlet velocity and structure parameters (diameter ratio, expansion angle and filter length) on the flow uniformity in the RDPF are investigated. Furthermore, the Fuzzy grey relational analysis (FGRA) is employed to make a weight analysis of the influences of structure parameters on the regeneration performance and pressure drop of the RDPF. The results show that the velocity uniformity in the RDPF can be improved by properly reducing the inlet velocity, diameter ratio or expansion angle θ1. The capture-regeneration volume ratio with 8-10 is appropriate range for the structural optimization. Finally, the expansion angle θ1 is the most important structure parameter for the filter regeneration performance (regeneration time R = 0.8467; regeneration efficiency R = 0.6849) and the diameter ratio is the most important structure parameter for the pressure drop at the capture-regeneration "balance point" (R = 0.9352).


Plasmablastic lymphoma clinically presenting in the urinary tract.
Plasmablastic lymphoma is a high-grade B-cell lymphoma that poses major diagnostic problems and carries an extremely poor prognosis. This tumor was first described in the oral cavity of HIV+ patients but has since been identified in other sites and in seronegative patients. We describe 2 cases of plasmablastic lymphoma of the urinary tract that both presented with hydronephrosis. One occurred in an HIV+ patient and harbored a MYC translocation; the other, in an HIV- patient with no translocation detected.


Microbiota transplantation: concept, methodology and strategy for its modernization.
Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.


A diagnostic challenge: acute generalized exanthematous pustulosis or pustular psoriasis due to terbinafine.
A 72-year-old man developed a generalized erythematous pustular eruption 11 weeks after commencing terbinafine. Clinically and histologically, the appearance was that of acute generalized exanthematous pustulosis (AGEP), and the disease was managed with topical preparations. Initial improvement was marred by relapse of acute pustulosis, now more in keeping with terbinafine-induced pustular psoriasis (PP), which was successfully treated with acitretin. This case highlights the difficulty of differentiating between AGEP and PP.


Therapeutic RNA-silencing oligonucleotides in metabolic diseases.
Recent years have seen unprecedented activity in the development of RNA-silencing oligonucleotide therapeutics for metabolic diseases. Improved oligonucleotide design and optimization of synthetic nucleic acid chemistry, in combination with the development of highly selective and efficient conjugate delivery technology platforms, have established and validated oligonucleotides as a new class of drugs. To date, there are five marketed oligonucleotide therapies, with many more in clinical studies, for both rare and common liver-driven metabolic diseases. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in metabolism, review past and current clinical trials, and discuss ongoing challenges and possible future developments.


Metrazole induction of c-fos and proenkephalin gene expression in the rat adrenal and hippocampus: pharmacological characterization.
We have previously reported that the administration of metrazole (MTZ) produces a sequential, dose-dependent induction of c-fos and proenkephalin (Penk) gene expression in the rat hippocampus and adrenal. The adrenal is more sensitive to induction of these genes by MTZ. In the present study, we have compared the induction of c-fos and Penk in the hippocampus and adrenal, and examined the consequences of selected pharmacological manipulations. Treatment with LY274614, a competitive NMDA-receptor antagonist, blocked MTZ-induced convulsions and the MTZ-induction of c-fos and PPenk mRNAs in the hippocampus, and PPenk mRNA in the adrenal. However, in the adrenal the MTZ-induction of c-fos was only partially inhibited by LY274614. A combination of peripheral acting cholinergic antagonists (chlorisondamine plus methylatropine) prevented the MTZ-induction of adrenal c-fos and PPenk mRNA without significant alterations in the MTZ-induction of hippocampal c-fos mRNA or convulsions. Trifluoperazine, a calcium/calmodulin inhibitor, attenuated the MTZ-induction of c-fos mRNA while potentiating the MTZ-induction of PPenk mRNA in both the hippocampus and the adrenal. These results demonstrate that the MTZ induction of c-fos and Penk gene expression in the rat adrenal can be modulated by drugs acting in the CNS at NMDA receptors, in the periphery at postsynaptic cholinergic receptors and intracellularly at the calcium/calmodulin signal transduction pathway. Furthermore, we provide additional evidence that MTZ-induction of c-fos and Penk mRNAs can be dissociated by drugs acting at these sites.


A multicomponent, random walk model of transport and metabolism inside a neuron.
A model of multicomponent transport, consumption, and production of metabolites inside a neuron containing discrete mitochondria and glycolytic enzymes is developed using a random walk model of molecular transport. The ratio of anaerobic to aerobic metabolism which maximizes ATP production under normal, ischemic, and anoxic conditions is calculated. The ratio of the number of mitochondria to glycolytic enzymes which maximizes ATP under normal conditions is also calculated. Because the volume of the neuron is fixed, the sum of the number of mitochondria and glycolytic enzymes is fixed. This constraint is incorporated in the optimization process as an interior penalty function. Some of the advantages of employing the random walk technique are simple stoichiometry can be used to model consumption and production of metabolites, the geometry of the enzyme system and their active sites can be easily included in the model, and saturation of enzymes can be more easily modeled.


Differential behavioral effects of ACTH 4-10 and [D-Phe7] ACTH 4-10.
Intraventricular administration of an access of ACTH 4-10 does not interfere with the excessive grooming behavior of rats, elicited by intraventricular administration of [D-Phe7] ACTH 4-10. In an avoidance extinction paradigm, the two ACTH analogs have opposite effects. ACTH 4-10 counteracts the facilitation of extinction seen after [D-Phe7] ACTH 4-10, only under conditions that treatment with ACTH 4-10 alone results in retardation of that extinction. The data are discussed in terms of a multiple interaction of these peptides with brain function.


Evaluation the results of anterior cruciate ligament reconstruction with or without using antibiotic solution during graft preparation.
Joint infection after Anterior Cruciate Ligament (ACL) reconstruction is an uncommon infection which can affect joint movement and function. In this study, the impact of using antibiotic during graft preparation on the results of ACL reconstruction was investigated to examine the negative effects of antibiotic solution on graft and clinical symptoms after the surgery. In this randomized clinical trial study, 80 patients were enrolled. In one group, the graft was placed in vancomycin solution (500 mg of vancomycin powder in 100 ml of normal saline) for 10-15 min during the surgery. In other group, the surgery was performed routinely and the graft was not placed in antibiotic solution. Intravenous antibiotic was given to both groups and they underwent ACL reconstruction surgery through arthroscopic transportal technique using their hamstring tendon. Symptoms and examinations of patients were evaluated for one year after the surgery. There was no difference between two groups in terms of knee dislocation, knee lock, pain, fever, positivity of Lachman test, Anterior drawer test and pivot-shift test, knee swelling, and movement restriction in flection and extension (P > 0.05). No infection was seen in patients. Placing grafts in vancomycin solution does not have negative effects on graft quality and results of ACL surgery.


Exploring the structural, photophysical and optoelectronic properties of a diaryl heptanoid curcumin derivative and identification as a SARS-CoV-2 inhibitor.
Developing modifiable natural products those having antiviral activities against SARS-CoV-2 is a key research area which is popular in current scenario of COVID pandemic. A diaryl heptanoid curcumin and its derivatives are already presenting promising candidates for anti-viral drug development. We have synthesized single crystals of a dimethylamino derivative of natural curcumin and structural characterization was done by single crystal XRD analysis. Using steady-state absorption and emission spectra and guided by complimentary ab initio calculations, we unraveled the solvent effects on the photophysical properties of the dimethyl amino curcumin derivative. Chemical reactivity of the compound has investigated using frontier molecular orbitals and molecular electrostatic potential surface. High stability of the curcumin derivative in water environment has evaluated by Radial Distributions Functions (RDF) calculated via Molecular Dynamics (MD) simulations. The inhibitory activity of the title compound was evaluated by in silico methods and the stability of the protein-ligand complexes were studied using Molecular Dynamics simulations and MM-PBSA analysis. With this detailed study, we hope to motivate scientific community to develop new curcumin derivatives against SARS-CoV-2 virus.


Morphology and mechanics of daughter cells "delaminating" from the ventricular zone of the developing neocortex.
During the development of the murine neocortex, time-lapse imaging and microsurgical experiments demonstrate that distinct mechanical forces may be acting on the migration of delaminating daughter cells. Bipolar daughter cells transform into a unipolar morphology as they detach from the inner ventricular surface along the embryonic cerebral wall. Twisting and stretching of their distally remaining pial process establishes a spring-like mechanism that efficiently pulls the soma of these transforming cells to the outer pial surface. The significance of this physical contraction observed in transforming bipolar cells is highlighted when compared to the migration of pin-like daughter cells that lack a pial process. While bipolar and pin-like cells each initially appear epithelial with a ventricular process integrated into the adherence junction meshwork at the ventricular surface, the pin-like cells instead show a transient adventricular somal movement. Consequently, pin-like cells exit from the ventricular zone much more slowly than bipolar cells. Thus, these contrasting movements of daughter cells suggest that differential pulling forces may act separately on their pial and ventricular processes as they delaminate from the telencephalic germinal zone.


Biodegradation of Laundry Wastewater Under Aerobic and Anaerobic Conditions: A Kinetic Evaluation.
This research was conducted in a batch mode in a laboratory-scale setup to study (1) the biodegradation of laundry wastewater under aerobic and anaerobic conditions and to quantify the degradation at steady-state in terms of kinetic parameters and (2) the inhibition caused by laundry wastewater on growth-substrate utilization by un-acclimated ethanol-enriched aerobic and anaerobic microbial cultures. The chemical oxygen demand (COD) removal was above 95% under aerobic condition; however, the COD removal varied between 70 and 88% under anaerobic condition. The steady-state kinetic parameters k, Ks, Y, μm, and kd were 1.75 d-1, 21.67 mg COD/L, 0.4 mg volatile suspended solids (VSS)/mg COD, 0.7 d-1, and 0.06 d-1 respectively under aerobic condition; corresponding values under anaerobic condition were 4.7 d-1, 173.67 mg COD/L, 0.06 mg VSS/mg COD, 0.3 d-1, and 0.04 d-1. Laundry wastewater caused a competitive inhibition at doses above 200 mg/L under aerobic and anaerobic conditions.


Medication Management of Neuropathic Pain Disorders.
It is important for Oral and Maxillofacial Surgeons to be familiar with the various neuropathic facial pain disorders and their appropriate treatments. Neuropathic pain can be characterized by the nature of the pain experienced by patients; episodic or continuous. Episodic neuropathic pain disorders include trigeminal neuralgia and glossopharyngeal neuralgia. Continuous neuropathic pain disorders compromise of disorders such as idiopathic trigeminal neuralgia, postherpetic neuralgia, central post-stroke pain, and complex regional pain syndrome. Various forms of pharmacologic management exist for these neuropathic pain disorders.


Microscopic and pulse cytophotometric investigation of a carcinoma of the jejumum in a seven year old child.
In a seven year old boy with acute abdominal pain and intestinal bleeding, laparotomy revealed an invaginated carcinoma adenomatosum cylindrocellulare in the distal part of the jejunum. Histological and pulse cytophotometric investigations support the diagnosis of a highly differentiated but locally destructive and malignant tumor.


Effect of levetiracetam in refractory childhood epilepsy syndromes.
In this open-label add-on study of levetiracetam in refractory childhood epilepsy syndromes, we studied the effect of a rapid introduction of levetiracetam on the total seizure frequency in 21 children, known to have partial and generalized seizures. Starting dosage was 10 mg/kg/day, increased every 4th day by 10 mg/kg up to a maximum of 60 mg/kg/day, depending on efficacy and tolerability. In this highly refractory population, 47% showed a seizure frequency reduction of more than 50%. Levetiracetam was effective both in partial and generalized seizures, with a significant effect on myoclonic seizures. Only mild side-effects were observed in four of 21 children, at a dosage of more than 40 mg/kg/day.


Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children.
The prevalence of nonneuropathic bladder/sphincter dysfunction was assessed with a questionnaire in 310 of the 386 children enrolled in the European branch of the International Reflux Study in Children. Despite the exclusion criteria (neuropathic bladder, anatomical malformations other than vesicoureteral reflux and overt dysfunctional voiding or urge incontinence), the prevalence of bladder/sphincter dysfunction was as high as 18%. Four patterns of dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. The questionnaire proved helpful in detecting low profile cases of bladder/sphincter dysfunction, as well as indicating the need for further urodynamic studies. A strong correlation was established between recurrences of urinary tract infections, as well as disappearance of vesicoureteral reflux (negative correlation) and nonneuropathic bladder/sphincter dysfunction. This finding implies that detection and treatment of bladder/sphincter dysfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux.


Identification and counting of fish targets using adaptive resolution imaging sonar.
Fish are a critical component of marine biology; therefore, the accurate identification and counting of fish are essential for the objective monitoring and assessment of marine biological resources. High-frequency adaptive resolution imaging sonar (ARIS) is widely used for underwater object detection and imaging, and it quickly obtains close-up video of free-swimming fish in high-turbidity water environments. Nonetheless, processing the massive data output using imaging sonars remains a major challenge. Here, the authors developed an automatic image-processing programme that fuses K-nearest neighbour background subtraction with DeepSort target tracking to automatically track and count fish. The automatic programme was evaluated using four test data sets with different target sizes and observation ranges and differently deployed sonars. According to the results, the approach successfully counted free-swimming fish targets with an accuracy index of 73% and a completeness index of 70%. Under appropriate conditions, this approach could replace time-consuming semi-automatic approaches and improve the efficiency of imaging sonar data processing, while providing technical support for future real-time data processing.


Provider support of spontaneous pushing during the second stage of labor.
To describe the association between provider communication and actual maternal pushing behavior in second-stage labor and to test differences in length of second stage and total maternal pushing time by maternal pushing behavior. Descriptive. Midwest hospital birth unit. Twenty primigravidas who gave birth vaginally. Type of provider communication (supportive of spontaneous or directed pushing). Maternal pushing behavior (spontaneous or directed) documented by videotape review. The percentage of provider communication supporting spontaneous pushing versus directed pushing and the percentage of actual spontaneous versus directed maternal pushing behavior were associated (Pearson r = .80, p = .001, for spontaneous and r = .89, p = .001, for directed). Neither duration of second stage (t = .06, p = .95) nor time spent pushing (t = .15, p = .89) differed by spontaneous versus directed pushing style. The proportion of spontaneous pushing by the birthing woman was positively and significantly associated with the proportion of caregiver communication supporting and encouraging spontaneous pushing. Importantly, spontaneous pushing did not significantly lengthen the duration of second-stage labor or total time spent pushing.


Changes in secondary outcomes associated with brief interventions for problem gambling in methadone patients.
Patients in methadone maintenance treatment (MMT) with problem gambling (PG) experience worse psychosocial outcomes than their non-PG counterparts. Interventions targeting PG in MMT may enhance psychosocial functioning beyond gambling reduction and abstinence. The present study was a secondary data analysis that examined the trajectories of non-gambling outcomes of three brief PG interventions (i.e., brief psychoeducation, brief advice, motivational enhancement therapy plus cognitive-behavioral therapy [MET + CBT]) among MMT patients. Participants (N = 109) were engaged in substance use disorder treatment, met criteria for PG, and had a current or lifetime history of MMT. Latent growth curve models examined outcome trajectories of psychiatric, medical, legal, employment, and social problems, as well as psychological distress and quality of life. Follow-up analyses examined clinically significant change. MET + CBT patients reported lower medical problems at baseline and over time than the brief interventions. There was no evidence of differences between interventions on the other outcomes. Psychiatric problems and psychological distress decreased over time for the entire sample, regardless of the PG intervention. About 24% and 13% of the sample demonstrated clinically significant improvements in psychological distress from baseline to 5 months, and 5 months to 12 months, respectively. Nearly 21% of the sample showed clinically significant improvements in psychiatric problems from 5 months to 12 months. Among all patients, men and those with more severe opioid dependence symptoms demonstrated the greatest psychological improvements. Many patients in MMT with PG experience improvements in psychological problems, including long-term improvement, regardless of the PG intervention offered.


Adolescent attendance at transcultural psychotherapy: a retrospective cohort study.
Migrant adolescents in therapy for psychological problems are at risk of poor attendance or even of dropping out. Transcultural psychotherapy has been developed in France to take cultural diversity into account in psychological treatment and to deal with the specific difficulties encountered in the psychotherapeutic treatment of this population. This study aims to assess adolescents' attendance rates to this form of psychotherapy and to explore the association of these rates with demographic, cultural, and clinical variables. We conducted a retrospective clinical cohort study of 148 adolescents aged from 11 to 20 years treated between 2008 and 2018 at two transcultural psychotherapy centers in Paris. Statistical analyses tested demographic, cultural, and clinical hypotheses. The main result was the high attendance rate at transcultural psychotherapy sessions among adolescents (77.8%). Attendance rates were not associated with age, gender, family size, generation of migration, or cultural area of origin, but were significantly linked to support in therapy, specifically, the presence at the first transcultural psychotherapy session of the first-line therapist, an interpreter, or both. Transcultural psychotherapy appears to be an effective method for addressing the complex symptoms experienced by migrant adolescents. Better attendance at sessions is statistically significantly associated with factors favoring a therapeutic alliance, specifically, the presence of the first-line therapist or an interpreter in TPT sessions and the existence of support from a social worker. The holistic approach of transcultural psychotherapy to adolescent care may explain the high attendance rates observed.


Iliopsoas haemorrhage complicated by femoral neuropathy in patients with haemophilia: a case series report.
The study aimed to determine the incidence of femoral neuropathy in patients with haemophilia exhibiting iliopsoas haemorrhage. Patients with iliopsoas haemorrhage confirmed by ultrasonography or CT scan were studied retrospectively. A total of 44 episodes of iliopsoas haemorrhage occurred in 20 patients with haemophilia (A17, B3). Most episodes in patients without inhibitors (14/16 = 87.5%) were adequately treated followed by prophylaxis. However, 11 of 28 episodes (39.3%) in patients with inhibitors were adequately treated and no prophylaxis was provided. An appropriate rehabilitation programme was arranged during hospitalisation and follow-up. Femoral neuropathy was observed in 28 of 44 episodes, while 16 episodes of persistent femoral neuropathy from previous bleeding were excluded. As a result, 11 of 28 episodes (39.3%) of femoral neuropathy were similarly found amongst patients with and without inhibitors. The mean time of onset and resolution of femoral neuropathy were 3.7 (1.8) and 23.4 (20.5) days after the onset of iliopsoas haemorrhage, respectively. Patients receiving inadequate and delayed replacement had a significantly higher rate of femoral neuropathy than those who received adequate and prompt replacement. Femoral neuropathy following iliopsoas haemorrhage was common in haemophilia patients with and without inhibitors.


Model-based analysis for the population pharmacokinetics of iberdomide and its major active metabolite in healthy subjects and patients with relapsed and refractory multiple myeloma.
A parent-metabolite population pharmacokinetic (popPK) model of iberdomide and its pharmacologically active metabolite (M12) was developed and the influence of demographic and disease-related covariates on popPK parameters was assessed based on data from 3 clinical studies of iberdomide (dose range, 0.1-6 mg) in healthy subjects (n = 81) and patients with relapsed and refractory multiple myeloma (n 245). Nonlinear mixed effects modelling was used to develop the popPK model based on data from 326 subjects across 3 clinical studies. The pharmacokinetics (PK) of iberdomide were adequately described with a 2-compartment model with first-order absorption and elimination. A first-order conversion rate was used to link the 1-compartment linear elimination metabolite model with the parent model. Subject type (multiple myeloma patients vs. healthy subject) was a statistically significant covariate on apparent clearance and apparent volume of distribution for the central compartment, suggesting different PK between patients with multiple myeloma and healthy subjects. Aspartate aminotransferase and sex were statistically but not clinically relevant covariates on apparent clearance. Metabolite (M12) PK tracked the PK of iberdomide. The metabolite to parent ratio was consistent across doses and combinations. The parent-metabolite population PK model adequately described the time course PK data of iberdomide and M12. Iberdomide and M12 PK exposure were not complicated by demographic factors (age [19-82 y], body weight [41-172 kg], body surface area [1.4-2.7 m2 ], body mass index [16.4-59.3 kg/m2 ]), combination (in combination with dexamethasone and daratumumab), mild hepatic, or mild and moderate renal impairments. The model can be used to guide the dosing strategy for special patient population and inform future iberdomide study design.


Downregulation of argininosuccinate synthase 1 (ASS1) is associated with hypoxia in placental development.
Argininosuccinate synthase (ASS1) is involved in nitric oxide production, which has a key role in placental development improving pregnancy outcomes. Syncytiotrophoblast and extravillous trophoblast differentiations are milestones of placental development and their impairment can cause pathologies, such as preeclampsia (PE) and fetal growth restriction (FGR). Immunohistochemistry and Western blotting were used to localize and quantify ASS1 in first trimester (8.2 ± 1.8 weeks), third trimester (38.6 ± 1.1 weeks), and PE (36.3 ± 1.5 weeks) placentas. In addition, cell cultures were used to evaluate ASS1 expression under hypoxic conditions and the syncytialization process. Our data showed that ASS1 is localized in the villous cytotrophoblast of first trimester, third trimester, and PE placentas, while the villous cytotrophoblast adjacent to the extravillous trophoblast of cell columns as well as the extravillous trophoblast were negative for ASS1 in first trimester placentas. In addition, ASS1 was decreased in third trimester compared to the first trimester placentas (p = 0.003) and no differences were detected between third trimester and PE placentas. Moreover, ASS1 expression was decreased in hypoxic conditions and syncytialized cells compared to those not syncytialized. In conclusion, we suggest that the expression of ASS1 in villous cytotrophoblast is related to maintaining proliferative phenotype, while ASS1 absence may be involved in promoting the differentiation of villous cytotrophoblast in extravillous cytotrophoblast of cell columns in first trimester placentas.


Analysis of the Association between Female Medical History and Thyroid Cancer in Women: A Cross-Sectional Study Using KoGES HEXA Data.
The purpose of this study was to evaluate the association between female medical history and thyroid cancer. Methods: Data from the Korean Genome and Epidemiology Study were collected from 2004 to 2016. Among a total of 1303 participants with thyroid cancer and 106,602 control (non-thyroid cancer) participants, the odds ratios (ORs) with 95% confidence intervals (CIs) of hysterectomy, oophorectomy, use of oral contraceptives, and number of children were evaluated. Results: The adjusted OR of hysterectomy for thyroid cancer was 1.73 (95% CI = 1.48-2.01, p < 0.001) in the minimally adjusted model. The adjusted ORs for thyroid cancer were 1.89 (95% CI = 1.06-3.37, p = 0.031), 0.89 (95% CI = 0.83-0.94, p < 0.001), and 0.85 (95% CI = 0.73-0.99, p = 0.040) for bilateral oophorectomy, number of children, and use of oral contraceptives, respectively, in the fully adjusted model. In the subgroup analysis, the adjusted ORs of bilateral oophorectomy were significant in the younger age (OR = 3.62, 95% CI = 1.45-9.03, p = 0.006), while the number of children was significant in the older age (OR = 0.86, 95% CI = 0.80-0.93, p < 0.001). Conclusions: The ORs of hysterectomy and bilateral oophorectomy were significantly higher in the thyroid cancer group in the younger age group. The adjusted ORs of the number of children were significantly low in the older age group.


Biodegradation of crude oil and pure hydrocarbons by extreme halophilic archaea from hypersaline coasts of the Arabian Gulf.
Two extreme halophilic Haloferax strains and one strain each of Halobacterium and Halococcus were isolated from a hypersaline coastal area of the Arabian Gulf on a mineral salt medium with crude oil vapor as a sole source of carbon and energy. These archaea needed at least 1 M NaCl for growth in culture, and grew best in the presence of 4 M NaCl or more. Optimum growth temperatures lied between 40 and 45 degrees C. The four archaea were resistant to the antibiotics chloramphenicol, cycloheximide, nalidixic acid, penicillin, streptomycin and tetracycline. The strains could grow on a wide scope of aliphatic and aromatic (both mono-and polynuclear) hydrocarbons, as sole sources of carbon and energy. Quantitative measurements revealed that these extreme halophilic prokaryotes could biodegrade crude oil (13-47%, depending on the strain and medium salinity), n-octadecane (28-67%) and phenanthrene (13-30%) in culture after 3 weeks of incubation. The rates of biodegradation by all strains were enhanced with increasing NaCl concentration in the medium. Optimal concentration was 3 M NaCl, but even with 4 M NaCl the hydrocarbon-biodegradation rates were higher than with 1 and 2 M NaCl. It was concluded that these archaea could contribute to self-cleaning and bioremediation of oil-polluted hypersaline environments.


Separating slow BOLD from non-BOLD baseline drifts using multi-echo fMRI.
The functional magnetic resonance (fMRI) baseline is known to drift over the course of an experiment and is often attributed to hardware instability. These ultraslow fMRI fluctuations are inseparable from blood oxygenation level dependent (BOLD) changes in standard single echo fMRI and they are therefore typically removed before further analysis in both resting-state and task paradigms. However, some part of these fluctuations may be of neuronal origin, as neural activity can indeed fluctuate at the scale of several minutes or even longer, such as after the administration of drugs or during the ultradian rhythms. Here, we show that it is possible to separate the slow BOLD and non-BOLD drifts automatically using multi-echo fMRI and multi-echo independent components analysis (ME-ICA) denoising by demonstrating the detection of a visual signal evoked from a flickering checkerboard with slowly changing contrast.


Homicide-suicide (dyadic death): a case study of double hanging.
Murder-suicide, homicide-suicide, and dyadic death all refer to an incident where a homicide is committed followed by the perpetrator's suicide almost immediately or soon after the homicide. Homicide-suicides are relatively uncommon and vary from region to region. In the selected literature that we reviewed, shooting was the common method of killing and suicide, and only 3 cases of homicidal hanging involving child victims were identified. We present a case of dyadic death where the method of killing and suicide was hanging, and the victim was a young woman.


A new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system.
Protective antigen (PA) is a nontoxic protein present in anthrax toxin. Domain 4 of PA (PA-D4) acts as a receptor binding site for tumor endothelial marker 8 (TEM8). In this study, KYND motif from PA-D4 was utilized as a ligand against TEM8. The efficiency of KYND motif on cellular association was assessed by evaluating the cellular uptake of PEGylated liposomes (PEG-LPs) in TEM8 positive and negative cells. The peptide was attached on the top of the PEG of PEG-LP. Compared to PEG-LP, KYND modified PEG-LP (KYND-PEG-LP) enhanced the cellular uptake to a greater extent in all cell lines. Based on the inhibition assay, no receptor involvement was observed in the cellular association of KYND-PEG-LP, suggesting that KYND motif functions as a cell penetrating peptide (CPP) which facilitated the internalization of PEG-LP via clathrin mediated endocytosis pathway. Further enhancement of cellular uptake was observed when KYND-PEG-LP was combined with octaarginine (R8) on the surface of lipid membrane as dual-CPP ligand formulation, however, when PEG-LP combined with only R8, only negligible enhancement was observed. These findings suggest that two CPP ligands act in a synergistic fashion; therefore the dual-CPP ligand based liposomal formulation can be assumed to be an effective delivery system.


Acute Myeloid Leukemia Presenting Less Than 3 Weeks After Living Donor Kidney Transplant: A Case Report.
Acute myeloid leukemia (AML) is a rare malignancy with increased incidence in the kidney transplantation (KT) population for which immunosuppression has been implicated as a putative cause. The average time interval from KT to AML development is 5 years. We present the case of a 61-year-old man who was found to have peripheral blood blasts on a postoperative day 20 routine blood draw after an uneventful unrelated living donor kidney transplant. He subsequently had a bone marrow biopsy and next-generation sequencing (NGS)-based molecular testing, which demonstrated AML characterized by SMC1A and TET2 mutations. He received induction chemotherapy followed by hematopoietic cell transplantation (HCT) from the kidney donor, who happened to be matched at one haplotype. At 12 months after his HCT and 15 months after his KT, his AML remained in remission, normal renal function was preserved, no active graft-versus-host disease was present, and immunosuppression was tapering. With full donor-derived hematopoietic chimerism, we expect to be able to discontinue immunosuppression shortly, thereby achieving tolerance. The short time interval between KT and development of AML suggests the malignancy was likely present before KT. Modern NGS-based analysis offers a promising method of identifying transplant candidates with unexplained hematologic abnormalities on pre-KT testing who may benefit from formal hematologic evaluation.


The Influence of Cognitive Status on Elder Food Choice and Meal Service Satisfaction.
This article describes the testing of a new nursing home food delivery system that empowers elders to choose the foods they want to eat and gives them an active voice in menu development. Using a 2-group, repeated measures design, 61 elderly residents from 2 eastern Washington nursing homes were recruited to participate in a 6-month study. Outcome measures included food and meal service satisfaction, body weight, serum prealbumin, and food intake. Serum prealbumin levels and body weight increased post intervention for treatment group residents. Mini-Mental Status Examination (MMSE) scores were not associated with the changes in serum prealbumin, body weight, or food intake. The MMSE scores did not influence the resident's ability to actively participate in the rate the food process or choose the foods they liked and preferred to eat. Cognitive impaired older adults experienced weight gain similarly to higher functioning elderly individuals.


An efficient online peak detection algorithm for synchronized intestinal electrical stimulation and its application for treating diabetes.
Obesity is one of leading risk factors for type 2 diabetes and other types of chronic diseases. Synchronized intestinal electrical stimulation (SIES) has been explored for treating obesity and diabetes. In SIES, electrical stimulation is delivered to the small intestine in synchronization with the intrinsic intestinal myoelectrical activity (its basic rhythm is called slow wave) and therefore, the accurate detection of intestinal slow waves is critically important for SIES. The aim of this study is to detect the peaks in intestinal slow waves in real-time based on the automatic multiscale peak detection (AMPD) method. In this paper, we introduce an efficient technique for real-time detection of peaks in intestinal slow waves. The presented method is based on peak estimation of a given quasi-periodic signal using the AMPD method. This method uses a multi-scale approach to identify the peaks of the intestinal slow waves with high detection accuracy and a minimal delay. Throughout the experiments, the multi-scale technique is used to estimate the quasi-periodic signals using different signal-to-noise ratio, λ (optimal scale), and the "lag" β (number of datapoints for right hand estimation) as important performance factors. The performance of the presented method is also calculated and utilized in the comparison process for 10 datasets of the intestinal slow waves from rats at λ = 150 ms and two values of β = 100 ms and 150 ms. The experimental results show that the presented method has good overall accuracy for online peak detection while maintaining low memory and computational complexity. Numerically, the overall accuracy is above 90%, and 98% for the rodent intestinal slow waves at a time-lag of 150 ms. The developed SIES system has been applied to successfully reduce postprandial blood glucose in a rodent model of hyperglycemia. In conclusion, the developed algorithm is adequate for on-line peak detection of the intestinal slow waves; the SIES method used the developed peak detection algorithm which is effective in reducing postprandial blood glucose in a rodent model of hyperglycemia.


Selection on adult female body size in rhesus macaques.
Body size is a critical descriptor of animal biology with many ecological, behavioral, and physiological correlates. Size differences among species or between populations are often explained by adaptive scenarios invoking the action of selection, although studies of selection in action on primate body size, or other phenotypic traits, are very rare. We document directional selection for larger skull and postcranial size in the skeletons of female semi-free ranging rhesus macaques (Macaca mulatta) from Cayo Santiago, born between 1957 and 1982. Larger females live to later ages and consequently give birth to more offspring. Despite selection for larger size, there are indications of a trend toward generally smaller size in the same birth cohorts. This trend is provisionally attributed to increasing population density, though other environmental factors may play a role. Small selection differentials and low heritabilities also limit the genetic response to selection. Alternative explanations for increasing adult size in the skull and postcranium, such as continued adult growth or pathological bone deposition, do not adequately explain the observed age-related trends and are inconsistent with longitudinal studies of adult skeletal change.


Corrigendum: Assessment of psychometric properties of the self-stigma inventory for Iranian families of persons who use drugs.
[This corrects the article DOI: 10.3389/fpubh.2022.1017273.].


Preparation of Neutral trans - cis [Ru(O2CR)2P2(NN)], Cationic [Ru(O2CR)P2(NN)](O2CR) and Pincer [Ru(O2CR)(CNN)P2] (P = PPh3, P2 = diphosphine) Carboxylate Complexes and their Application in the Catalytic Carbonyl Compounds Reduction.
The diacetate complexes trans-[Ru(κ1-OAc)2(PPh3)2(NN)] (NN = ethylenediamine (en) (1), 2-(aminomethyl)pyridine (ampy) (2), 2-(aminomethyl)pyrimidine (ampyrim) (3)) have been isolated in 76-88% yield by reaction of [Ru(κ2-OAc)2(PPh3)2] with the corresponding nitrogen ligands. The ampy-type derivatives 2 and 3 undergo isomerization to the thermodynamically most stable cationic complexes [Ru(κ1-OAc)(PPh3)2(NN)]OAc (2a and 3a) and cis-[Ru(κ1-OAc)2(PPh3)2(NN)] (2b and 3b) in methanol at RT. The trans-[Ru(κ1-OAc)2(P2)2] (P2 = dppm (4), dppe (5)) compounds have been synthesized from [Ru(κ2-OAc)2(PPh3)2] by reaction with the suitable diphosphine in toluene at 95 °C. The complex cis-[Ru(κ1-OAc)2(dppm)(ampy)](6) has been obtained from [Ru(κ2-OAc)2(PPh3)2] and dppm in toluene at reflux and reaction with ampy. The derivatives trans-[Ru(κ1-OAc)2P2(NN)] (7-16; NN = en, ampy, ampyrim, 8-aminoquinoline; P2 = dppp, dppb, dppf, (R)-BINAP) can be easily synthesized from [Ru(κ2-OAc)2(PPh3)2] with a diphosphine and treatment with the NN ligands at RT. Alternatively these compounds have been prepared from trans-[Ru(OAc)2(PPh3)2(NN)] by reaction with the diphosphine in MEK at 50 °C. The use of (R)-BINAP affords trans-[Ru(κ1-OAc)2((R)-BINAP)(NN)] (NN = ampy (11), ampyrim (15)) isolated as single stereoisomers. Treatment of the ampy-type complexes 8-15 with methanol at RT leads to isomerization to the cationic derivatives [Ru(κ2-OAc)P2(NN)]OAc (8a-15a; NN = ampy, ampyrim; P2 = dppp, dppb, dppf, (R)-BINAP). Similarly to 2, the dipivalate trans-[Ru(κ1-OPiv)2(PPh3)2(ampy)] (18) is prepared from [Ru(κ2-OPiv)2(PPh3)2] (17) and ampy in CHCl3. The pincer acetate [Ru(κ1-OAc)(CNNOMe)(PPh3)2] (19) has been synthesized from [Ru(κ2-OAc)2(PPh3)2] and HCNNOMe ligand in 2-propanol with NEt3 at reflux. In addition, the dppb pincer complexes [Ru(κ1-OAc)(CNN)(dppb)] (CNN = AMTP (20), AMBQPh (21)) have been obtained from [Ru(κ2-OAc)2(PPh3)2], dppb, and HAMTP or HAMBQPh with NEt3, respectively. The acetate NN and pincer complexes are active in transfer hydrogenation with 2-propanol and hydrogenation with H2 of carbonyl compounds at S/C values of up to 10000 and with TOF values of up to 160000 h-1.


Predictors of the evolution towards schizophrenia or mood disorder in patients with schizophreniform disorder.
In this study, 56 patients affected by schizophreniform disorder (SFD), as their first lifetime mental disorder, were re-evaluated 7.9+/-4.7 yrs (2-17 yrs) after their first hospitalization. At follow-up, schizophrenia (SC) was diagnosed in 25 patients (46%), a mood disorder (MD) in 19 (35%), a non-SC psychotic disorder in 10 (18%) and no disorder in 2 (4%). The evolution towards SC was predicted by the presence of blunted affect (OR: 1.88) and by poor pre-morbid functioning (OR: 1.10) at the index hospitalization. Our data suggest that SFD may represent the first psychotic presentation of different disorders and the evolution towards SC or a MD seems to be influenced by the pre-morbid level of functioning and by the presence of blunted affect.


Pathophysiology of Typical Atrial Flutter.
Nowadays, the pathophysiology mechanism of initiation and maintenance of reentrant arrhythmias, including atrial flutter, is well characterized. However, the anatomic and functional elements of the macro reentrant arrhythmias are not always well defined. In this article, we illustrate the anatomic structures that delineate the typical atrial flutter circuit, both clockwise and counterclockwise, paying attention to the inferior vena cava-tricuspid isthmus (CTI) and crista terminalis crucial role. Finally, we describe the left atrial role during typical atrial flutter, electrophysiologically a by-stander but essential in the phenotypic electrocardiogram (ECG).


Cloning and DNA sequence analysis of a Lactococcus bacteriophage lysin gene.
A gene for the lysin of Lactococcus lactis bacteriphage phi vML3 was cloned using an Escherichia coli/bacteriophage lambda host-vector system. The gene was detected by its expression of antimicrobial activity against L. lactis cells in a bioassay. The cloned fragment was analysed by sub-cloning on to E. coli plasmid vectors and by restriction endonuclease and deletion mapping. Its entire DNA sequence was determined and an open reading frame for the lysin structural gene was identified. The sequenced lysin gene would express a protein of 187 amino acids with a molecular weight of 21,090, which is in good agreement with that of a protein detected after in vitro transcription and translation of DNA encoding the gene. Expression of the lysin gene in E. coli and B. subtilis from an adjacent bacteriophage promoter was readily detected but in L. lactis expression of lysin was found to be lethal. The bacteriophage phi vML3 lysin had sequence homology with protein 15 of B. subtilis bacteriophage PZA. This protein is involved in DNA packaging during bacteriophage maturation rather than in host cell lysis. The cloning and analysis of the phi vML3 lysin gene is of importance in further understanding lactic streptococcal bacteriophages, for the development of positive selection vectors and for biotechnological applications of relevance to the dairy industry.


Reliable measurement of plasma kinin peptides: Importance of preanalytical variables.
The kallikrein-kinin system is involved in many (patho)physiological processes and kinin peptides are considered potential clinical biomarkers. Variance in blood specimen collection and processing, artificial ex vivo bradykinin formation, and rapid degradation of kinins have contributed to divergence in published plasma levels, therefore limiting their significance. Thus, reliable preanalytical settings are highly required. This study aimed to develop and evaluate a standardized preanalytical procedure for reliable kinin quantification. The procedure was based on identification of the most impactful variables on ex vivo plasma level alterations. Suitable protease inhibitors and blood specimen collection and handling conditions were systematically investigated. Their influence on plasma levels of seven kinins was monitored using an established in-house liquid chromatography-tandem mass spectrometry platform. In nonstandardized settings, ex vivo rise of bradykinin was found to already occur 30 seconds after blood sampling with high interindividual variation. The screening of 17 protease inhibitors resulted in a customized seven-component protease inhibitor, which efficiently stabilized ex vivo kinin levels. The reliability of kinin levels was substantially jeopardized by prolonged rest time until centrifugation, phlebotomy methodology (eg, straight needles, catheters), vacuum sampling technique, or any time delays during venipuncture. The subsequently developed standardized procedure was applied to healthy volunteers and proved it significantly limited interday and interindividual kinin level variability. The developed procedure for blood specimen collection and handling is feasible in clinical settings and allows for determination of reliable kinin levels. It may contribute to further elucidating the role of the kallikrein-kinin system in diseases like angioedema, sepsis, or coronavirus disease 2019.


Pex30 undergoes phosphorylation and regulates peroxisome number in Saccharomyces cerevisiae.
Pex30 is a dysferlin domain-containing protein whose role in peroxisome biogenesis has been studied by several research groups. Notably, recent studies have linked this protein to peroxisomes, endoplasmic reticulum and lipid bodies in Saccharomyces cerevisiae. Phosphoproteome studies of S. cerevisiae have identified several phosphorylation sites in Pex30. In this study we expressed and purified Pex30 from its native host. Analysis of the purified protein by circular dichroism spectroscopy showed that it retained its secondary structure and revealed primarily a helical structure. Further phosphorylation of Pex30 at three residues, Threonine 60, Serine 61 and Serine 511 was identified by mass spectrometry in this study. To understand the importance of this post-translational modification in peroxisome biogenesis, the identified residues were mutated to both non-phosphorylatable (alanine) and phosphomimetic (aspartic acid) variants. Upon analysis of the mutant variants by fluorescence microscopy, no alteration in the localization of the protein to ER and peroxisomes was observed. Interestingly, reduced number of peroxisomes were observed in cells expressing phosphomimetic mutations when cultured in peroxisome-inducing conditions. Our data suggest that phosphorylation and dephosphorylation of Pex30 may promote distinct interactions essential in regulating peroxisome number in a cell.


Glucose biosensor based on Au nanoparticles-conductive polyaniline nanocomposite.
In this paper, we report a novel glucose biosensor based on composite of Au nanoparticles (NPs)-conductive polyaniline (PANI) nanofibers. Immobilized with glucose oxidase (GOx) and Nafion on the surface of nanocomposite, a sensitive and selective biosensor for glucose was successfully developed by electrochemical oxidation of H2O2. The glucose biosensor shows a linear calibration curve over the range from 1.0x10(-6) to 8.0x10(-4) mol/L, with a slope and detection limit (S/N=3) of 2.3 mA/M and 5.0x10(-7) M, respectively. In addition, the glucose biosensor system indicates excellent reproducibility (less than 5% R.S.D.) and good operational stability (over 2 weeks).


Mortality and renal outcomes of patients with severe COVID-19 treated in a provisional intensive care unit.
COVID-19 has created an enormous health crisis and this spring New York City had a severe outbreak that pushed health and critical care resources to the limit. A lack of adequate space for mechanically ventilated patients induced our hospital to convert operating rooms into critical care areas (OR-ICU). A large number of COVID-19 will develop acute kidney injury that requires renal replacement therapy (RRT). We included 116 patients with COVID-19 who required mechanical ventilation and were cared for in our OR-ICU. At 90 days and at discharge 35 patients died (30.2%). RRT was required by 45 of the 116 patients (38.8%) and 18 of these 45 patients (40%) compared to 17 with no RRT (23.9%, ns) died during hospitalization and after 90 days. Only two of the 27 patients who required RRT and survived required RRT at discharge and 90 days. When defining renal recovery as a discharge serum creatinine within 150% of baseline, 68 of 78 survivors showed renal recovery (87.2%). Survival was similar to previous reports of patients with severe COVID-19 for patients cared for in provisional ICUs compared to standard ICUs. Most patients with severe COVID-19 and AKI are likely to recover full renal function.


An Mg-MOFs based multifunctional medicine for the treatment of osteoporotic pain.
Bone pain is the primary problem for patients with osteoporosis. Ketoprofen is clinically used to treat osteoporotic pain, while long-term oral administration of ketoprofen can cause some side effects. In addition, osteoporosis is also accompanied by bone mass loss and inflammation. In this study, we designed a multifunctional drug (Ket@Mg-MOF-74) adopted Mg-MOF-74 to load ketoprofen to treat osteoporotic pain, bone loss and inflammation comprehensively. Mg-MOF-74 was prepared, and the physicochemical characterization proved that it had excellent physical and chemical stability. Ket@Mg-MOF-74 was synthesized by post-synthetic modification method and a high loading rate of ketoprofen was confirmed. Drug release and ion release experiments indicated Ket@Mg-MOF-74 had a good controlled release of ketoprofen and Mg in solution. Cell experiments in vitro proved the compound drug could significantly reduce the expression of pain-related genes of cyclooxygenase 2 (COX2), obviously up-regulated the expression of osteogenic cytokines and remarkably down-regulated the secretion of pro-inflammatory factors. Therefore, Ket@Mg-MOF-74 is believed a promising painkiller for osteoporotic bone pain, with the function of anti-inflammatory and promoting bone formation.


Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial.
Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.


Tamoxifen use and acute pancreatitis: A population-based cohort study.
Several case reports have indicated that tamoxifen induced acute pancreatitis (AP); but no pharmacoepidemiological data support the claim. Therefore, we investigated whether tamoxifen use is correlated with the risk of AP in patients with breast cancer. This population-based cohort study used the Taiwan National Health Insurance Research Database. A cohort of 22 005 patients aged ≥20 years with breast cancer from January 1, 2000 to December 31, 2009 was identified and the date of cancer diagnosis was set as the index date. The end point was developing AP during the follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to determine the correlation between the risk of AP and tamoxifen use. Because the drug use varied over time, it was measured as a time-dependent covariate in the Cox proportional hazard model. The same approaches were applied in PS-matched cohorts. After adjustment for covariates and medication use including fluorouracil and doxorubicin, the risk of AP was not significant between tamoxifen users and tamoxifen nonusers (adjusted HR = 0.94, 95% CI = 0.74-1.19) in the non-matching cohorts. The results revealed no dose-response trend between tamoxifen use and the risk of AP (adjusted HR = 0.98, 95% CI = 0.96-1.00). The comorbidities DM and gallstones were associated with a significantly increased risk of AP. Similar trends were observed in PS-matched cohorts. No significant correlation was observed between tamoxifen use and the risk of AP in patients with breast cancer.


Sarcoid-like Uveitis with or without Tubulointerstitial Nephritis during COVID-19.
To report sarcoid-like uveitis with or without tubulointerstitial nephritis (TIN) during coronavirus disease 2019 (COVID-19) and to discuss diagnostic evaluation and treatment. Detailed information on the subject's demographics, medical history, ophthalmic examination findings, and laboratory results were obtained from medical records. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) images were evaluated. All seven patients aged between 8 and 17 had bilateral granulomatous panuveitis. TIN preceded in four patients. Thorax computed tomography of patient 1 was found to be compatible with COVID-19, patients 2 and 3 were in contact with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive parents, patients 4 and 5 were found to be SARS-CoV-2 PCR positive, and patients 6 and 7 were positive for SARS-CoV-2 IgG antibodies. ICGA revealed hypofluorescent dots in six patients. Intraocular inflammation was controlled with corticosteroid and/or immunomodulatory therapy. Visual acuity was maintained or improved in all. SARS-CoV-2 infection may be related to sarcoid-like uveitis and acute tubulointerstitial nephritis.


Myocardial systolic strain is decreased after aortic valve replacement in patients with aortic insufficiency.
Left ventricular three-dimensional nonlinear systolic strain determinations have potential to detect small decrements in ventricular function in patients with aortic insufficiency before and after aortic valve replacement. Magnetic resonance imaging with tissue-tagging was performed on 42 normal volunteers and 14 patients with chronic aortic insufficiency both before and 28 +/- 11 months after aortic valve replacement. Preoperative and postoperative left ventricular volume, dimensions and ejection fraction were determined for all subjects. Left ventricular systolic radial, circumferential, longitudinal, and minimum principal strain were calculated for six left ventricular regions. After aortic valve replacement, left ventricular volume and dimensions decreased significantly (p < 0.001) and ejection fraction increased nonsignificantly (p = 0.096). Strain values in preoperative aortic insufficiency patients did not differ significantly from controls. At an average of 28 +/- 11 months postoperatively, however, regional three-dimensional minimum principal and longitudinal strain was decreased in all six ventricular regions as well as globally (p < 0.03) compared with normal control values. Circumferential strain was significantly decreased globally and in all but two regions (p < 0.03). These magnetic resonance imaging-based techniques are sensitive enough to detect a previously unrecognized, significant decrease in both global and regional three-dimensional left ventricular systolic strain 2 years after aortic valve replacement for minimally symptomatic chronic aortic insufficiency despite improvement in ejection fraction and a decrease in left ventricular size. The reasons for a significant decline in left ventricular systolic strain after successful aortic valve replacement in minimally symptomatic chronic aortic insufficiency patients are not clear and warrant further investigation.


[Progress on the molecular mechanism and research methods of the interaction between cell and silk fibroin material].
This paper took silk fibroin material as an example to explain the effect of a variety of physical and chemical properties of the silk material on cell adhesion and reviewed the molecular mechanism between cell and materials in tissue engineering in recent years. According to this, the present paper outlines a set of research systems to explore the interaction between cell and material in tissue engineering.


An unusual complication from a functioning indwelling urethral catheter: case report of an abdominal mass.
A heretofore unreported complication from an indwelling catheter is presented. A catheter bulb became incarcerated in a bladder diverticulum and was misdiagnosed subsequently as an incarcerated umbilical hernia. The probable pathophysiological mechanism by which this event occurred is discussed.


Simple risk score for prediction of haemorrhagic complications after a percutaneous renal biopsy.
To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys. The risk score was derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers. The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre-biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre-biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A score for pre-biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low-risk 0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post-biopsy US findings increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk 2.7%, high-risk 16.9%). The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.


Short latency somatosensory-evoked potentials in children--Part 3. Findings following head injury.
Fourteen children aged 3 to 11 years who suffered from coma for at least 6 hours had somatosensory-evoked potential studies performed within 24 hours of neurotrauma. The upper cervical (Cv2) and bilateral cortical somatosensory-evoked potentials were recorded for calculation of the central somatosensory conduction time. Despite the fact that the SEP recordings were performed in the intensive care unit and the patients were receiving opiate and barbiturate therapy, satisfactory somatosensory-evoked potentials were recorded in all patients. Symmetrical short latency cortical somatosensory-evoked potentials were recorded bilaterally in 10 patients. Two patients with hemorrhagic cerebral contusions and unilateral cerebral edema had ipsilateral abnormalities of the cortical somatosensory-evoked potential. These patients all had normal central somatosensory conduction times and all had satisfactory neurological recoveries, although the two patients with abnormal cortical somatosensory-evoked potentials had focal neurological deficits. Two patients whose head injuries were complicated by hypoxia and refractory intracranial hypertension had bilaterally abnormal cortical somatosensory-evoked potentials, and both had vegetative outcomes. There was no correlation between the Glasgow Coma Score and central somatosensory conduction time; however, the number of components to the cortical somatosensory-evoked potential was related to the Glasgow Coma Score. The results suggest that the recording of somatosensory-evoked potentials can provide useful information about the functional status of central and cortical somatosensory pathways in children following major head injury.


Dikaryosis: genetic determination in Schizophyllum.
A dominant gene, dik(+), has been identified as responsible for the establishment of the dikaryon in the basidiomycetous fungus Schizophyllum commune. Interaction between compatible homokaryons, both of which carry the recessive allele dik, leads to the formation of a diploid mycelium that closely resembles the homokaryon in morphology.


Nonenzymatic amperometric determination of glucose by CuO nanocubes-graphene nanocomposite modified electrode.
Here, we report a nonenzymatic amperometric glucose sensor based on copper oxide (CuO) nanocubes-graphene nanocomposite modified glassy carbon electrode (CuO-G-GCE). In this case, the graphene sheets were cast on the GCE directly. CuO nanocubes were obtained by oxidizing electrochemically deposited Cu on the graphene. The morphology of CuO-G nanocomposite was characterized by scanning electron microscopy. The CuO-G-GCE-based sensor exhibited excellent electrocatalytic activity and high stability for glucose oxidation. Under optimized conditions, the linearity between the current response and the glucose concentration was obtained in the range of 2μM to 4mM with a detection limit of 0.7μM (S/N=3), and a high sensitivity of 1360μAmM(-1)cm(-2). The proposed electrode showed a fast response time (less than 5s) and a good reproducibility. The as-made sensor was applied to determine the glucose levels in clinic human serum samples with satisfactory results. In addition, the effects of common interfering species, including ascorbic acid, uric acid, dopamine and other carbohydrates, on the amperometric response of the sensor were investigated and discussed in detail.


Therapeutic perspective for children and young adults living with thalassemia and sickle cell disease.
Hemoglobinopathies, including thalassemias and sickle cell disease, are the most common monogenic diseases worldwide, with estimated annual births of more than 330,000 affected infants. Hemoglobin disorders account for about 3.4% of deaths in children under 5 years of age. The distribution of these diseases is historically linked to current or previously malaria-endemic regions; however, immigration has led to a worldwide distribution of these diseases, making them a global health problem. During the last decade, new treatment approaches and novel therapies have been proposed, some of which have the potential to change the natural history of these disorders. Indeed, the first erythroid maturation agent, luspatercept, and gene therapy have been approved for beta-thalassemia adult patients. For sickle cell disease, molecules targeting vaso-occlusion and hemoglobin S polymerization include crizanlizumab, which has been approved for patients ≥ 16 years, voxelotor approved for patients ≥ 12 years, and L-glutamine for patients older than 5 years. Conclusion: We herein present the most recent advances and future perspectives in thalassemia and sickle cell disease treatment, including new drugs, gene therapy, and gene editing, and the current clinical trial status in the pediatric populations. What is Known: • Red blood cell transfusions, iron chelation therapy and hematopoietic stem cell transplantation have been the mainstay of treatment of thalassemia patients for decades. • For sickle cell disease, until 2005, treatment strategies were mostly the same as those for thalassemia, with the option of simple transfusion or exchange transfusion. In 2007, hydroxyurea was approved for patients ≥ 2 years old. What is New: • In 2019, gene therapy with betibeglogene autotemcel (LentiGlobin BB305) was approved for TDT patients ≥ 12 years old non β0/β0 without matched sibling donor. • Starting from 2017 several new drugs, such as L-glutamine (approved only by FDA), crizanlizumab (approved by FDA and EMA for patients ≥ 16 years), and lastly voxelotor (approved by FDA and EMA for patients ≥ 12 years old).


Ability of three pharmacokinetic equations to predict steady-state serum theophylline concentrations in pediatric patients.
The pharmacokinetic equations of Chiou, Koup, and Kurland are often used in the pediatric setting to predict steady-state theophylline clearance using non-steady serum theophylline concentrations. However, these equations have not been validated or compared in a pediatric population. We evaluated the ability of these equations to predict steady-state serum theophylline concentrations in 61 children (0.21-14.3 years) who received a continuous intravenous theophylline (0.79 +/- 0.12 mg/kg/h) infusion for a minimum of five half-lives. Theophylline concentrations used in the Kurland equation were obtained 10.8 +/- 4.5 h after initiation of therapy and the time between the two concentrations used in the Chiou and Koup equations was 9.2 +/- 3.9 h. Predicted steady-state theophylline concentration values for the three methods were not different from each other (p = 0.91), nor were they different from the observed steady-state concentration values (p = 0.92). The coefficient of determination for predicted vs. observed steady-state concentrations was statistically significant (p less than 0.001) and was comparable for the three methods. There was no difference in mean bias (p = 0.78), precision (p = 0.82), or % error (p = 0.86) values for the three methods. Regardless of the method used, 75 to 82% of all predicted theophylline concentrations were within 20% of the observed steady-state value. However, on average, all methods underpredicted the clearance and hence overpredicted the serum theophylline concentration. The Kurland method did not predict steady-state concentrations any better in patients who had received theophylline prior to admission.(ABSTRACT TRUNCATED AT 250 WORDS)


A systematic review on Zhilong Huoxue Tongyu capsule in treating cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms and clinical outcomes.
Cardiovascular and cerebrovascular diseases have become a severe threat for human health worldwide, however, optimal therapeutic options are still developed. Zhilong Huoxue Tongyu capsule (ZL capsule) is mainly composed of Astragalus membranaceus, Leech, Earthworm, Cinnamomum cassia and Sargentodoxa cuneata, having functions of replenishing qi and activating blood, dispelling wind and reducing phlegm. It is an expanded application on the basis of traditional uses of above TCMs, acquiring a satisfactory curative effect on cardiovascular and cerebrovascular diseases over twenty years. To comprehensively summarize the main components of ZL capsule, understand the mechanisms of ZL capsule, and conclude clinical regimens of ZL capsule for cardiovascular and cerebrovascular diseases. We selected network pharmacology technology to analyze main active compounds and predict underlying mechanism of ZL capsule against atherosclerosis. Molecular docking was performed to simulate the interaction pattern between the active components of ZL capsule and putative targets. Further, PubMed, Web of Science, China National Knowledge Infrastructure and Google Scholar were used to search literatures, with the key words of "Zhilong Huoxue Tongyu capsule", "cardiovascular and cerebrovascular diseases", "atherosclerosis", "clinical study" and their combinations, mainly from 2000 to 2020. Both network pharmacology analysis, molecular docking and animal experiments studies confirmed that mechanisms of ZL capsule plays the role of anti-inflammatory, anti-apoptosis and promoting angiogenesis in treating cardiovascular and cerebrovascular diseases by multi-components acting on multi-targets via multi-pathways. Over 1000 clinical cases were benefited from the treatment of ZL capsule, suggesting a holistic concept of "the same therapy for different myocardial and cerebral diseases". For the first time, this systematic review may supply meaningful information for further studies to explore material basis and pharmacodynamics of ZL capsule and also provide a basis for sharing the "Chinese patent medicine" for cardiovascular and cerebrovascular diseases.


Improving the HIV Prevention Landscape to Reduce Disparities for Black MSM in the South.
Black men who have sex with men (MSM) in the South have the highest rates of HIV diagnosis in the country adding to the persistent racial disparities in HIV experienced by this population. The current HIV prevention and care landscape is heavily driven by individual-level clinical and biomedical approaches that have shown progress in reducing HIV diagnoses, but yield less than adequate results in reducing the HIV racial disparities for Black MSM in the South. In efforts to enhance focus on reducing the racial HIV disparities and more completely address the needs of Black MSM in the South, we offer insight on comprehensive approaches that can complement our current HIV prevention and care portfolio. There are five domains we discuss which include: (1) leveraging and integrating resources; (2) building upon existing program models designed to reduce disparities; (3) workforce development and cultural sensitivity; (4) social determinants of health data utilization; and 5) policy considerations. We urge public health practitioners and healthcare providers to consider and incorporate the outlined approaches to improve HIV outcomes along the continuum of care and ultimately reduce disparities in HIV affecting the quality of life of Black MSM living in the South.


Mitotic phosphorylation of Tau/MAPT modulates cell cycle progression in prostate cancer cells.
Tau/MAPT (microtubule associated protein tau) protein is actively studied for the pathologic consequences of its aberrant proteostasis in central nervous system leading to neurodegenerative diseases. Besides its ability to generate insoluble toxic oligomers, Tau homeostasis has attracted attention for its involvement in the formation of the mitotic spindle. This evidence, in association with the description of Tau expression in extra-neuronal tissues, and mainly in cancer tissues, constitutes the rationale for a more in-depth investigation of Tau role also in neoplastic diseases. In our study, we investigated the expression of phosphorylated Tau in prostate cancer cell lines with particular focus on the residue Thr231 present in microtubule binding domain. The analysis of prostate cancer cells synchronized with nocodazole demonstrated that the expression of Tau protein phosphorylated at residue Thr231 is restricted to G2/M cell cycle phase. The phosphorylated form was unable to bind tubulin and it does not localize on mitotic spindle. As demonstrated by the use of specific inhibitors, the phosphorylation status of Tau is under the direct control of cdk5 and PP2A, while cdk1 activation was able to exert an indirect control. These mechanisms were also active in cells treated with docetaxel, where counteracting the expression of the dephosphorylated form, by kinase inhibition or protein silencing, determined resistance to drug toxicity. We hypothesize that phosphorylation status of Tau is a key marker for G2/M phase in prostate cancer cells and that the forced modulation of Tau phosphorylation can interfere with the capacity of cell to efficiently progress through G2/M phase.


Selective loss of glucose-induced amplification of insulin secretion in mouse pancreatic islets pretreated with sulfonylurea in the absence of fuels.
The beta cell metabolism of glucose, and some other fuels, initiates insulin secretion by closure of ATP-sensitive K+ channels and amplifies the secretory response via unknown metabolic intermediates. The aim of this study was to further characterise the mechanism responsible for the metabolic amplification of insulin secretion. Pancreatic islets were isolated from albino mice by collagenase digestion. Insulin secretion in perifused islets was determined by ELISA. Bioluminometry was used to determine the ATP and ADP content of the incubated islets. After perifusing islets for 60 min with 2.7 micromol/l glipizide (closing all ATP-sensitive K+ channels) in the absence of any fuel, perifusion with a test medium containing 2.7 micromol/l glipizide plus 30 mmol/l glucose did not enhance insulin secretion. However, test media supplemented with 2.7 micromol/l glipizide plus either 10 mmol/l alpha-ketoisocaproate or 10 mmol/l 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid amplified the glipizide-induced insulin secretion. In pancreatic islets preincubated for 60 min with 2.7 micromol/l glipizide in the absence of any fuel, 40 min incubations in the presence of 2.7 micromol/l glipizide plus 30 mmol/l glucose or plus 10 mmol/l alpha-ketoisocaproate produced an increase in the ATP content, no change in the ADP content and a rather small increase in the ATP:ADP ratio. The corresponding effects of glucose and alpha-ketoisocaproate were similar. These results suggest that metabolic amplification of fuel-induced insulin secretion is not mediated by changes in the beta cell content of ATP and ADP, but might be due to export of citrate cycle intermediates to the beta cell cytosol.


Improved oxygenation during thoractomy with selective PEEP to the dependent lung.
In 22 patients during thoracotomy in the lateral position, the effects of selective positive end-expiratory pressure (PEEP) to the dependent lung while simultaneously ventilating the non-dependent lung at zero end-expiratory pressure (ZEEP) on (1) inspired O2 concentration required to maintain adequate Pao2 during thoractomy and 2) alveolar-arterial oxygen difference (AaO2D) while breathing 100 percent O2 at the end of thoractomy were examined and compared to ventilation of both lungs at ZEEP, Selective PEEP to the dependent lung resulted in adequate PaO2 with a lower inspired O2 concentration (44 +/- SD 6% versus 70 +/- SD 21%), and a smaller AsO2D while breathing 100 percent O2 189 +/- SD 31 versus 342 +/- SD 69 torr) at the end of thoracotomy.


[Functional analysis of novel mutations in PAX9 associated with familial oligodontia].
To gain new insights into the molecular pathogenesis of the 109(InsG) and 139(C--> T) mutations and their roles in familial oligodontia. The region of PAX9 paired domain (PAX9PD) was amplified and the expression plasmids were constructed in pGEXlambda -1T by PCR-based cloning. PAX9PD proteins were prepared on the basis of GST instruction. The binding of wild type and two novely mutant PAX9 paired domain to double-stranded DNA targets were analyzed by gel mobility shift assay. Wild type PAX9PD protein bind to the high affinity paired domain recognition sequences, CD19-2(A-ins) and Pax6CON, the 109(InsG) and 139(C--> T) mutant PAX9PD protein were unable to bind to these cognate DNA-binding sites. The functional defects in DNA binding of mutant 109(InsG) PAX9 and 139(C--> T) PAX9, as well as loss-of-function of PAX9 most likely result in its haploinsufficiency during the patterning of dentition and the subsequent loss of posterior teeth.


Expression of red cell Bga antigen in children. Lack of correlation with previous EB virus infection.
The red cell Bga antigen and the presence of EB virus antibody were determined in a group of children of mixed ages. Evidence of previous infection with EB virus does not correlate with the degree of expression of the Bga antigen on red cells.


Platelet function in neonates and children.
Platelets are major regulators of haemostasis and coagulation. The primary role of platelets in coagulation is to form a stable clot and stop bleeding. Studies of platelet phenotype and function in neonates and children have been restricted by the large volumes required for many common platelet function tests such as platelet aggregometry. Developmental changes in platelets have not been as well described as developmental changes in plasma coagulation proteins, and overall, platelet phenotype and function in neonates and children has been understudied when compared to adults. Recent developments in more sensitive platelet function testing methods requiring smaller blood volumes such as flow cytometry has enabled recent studies to further investigate platelet phenotype and function in neonates and children. In this review we will provide an overview of recent advances from the past five years in platelets in the context of developmental haemostasis, as well as the role of platelets in neonatal paediatric disease.


Amidoximated wooden solar evaporator for high-efficiency nuclear wastewater treatment.
The efficient removal of uranium (VI) (UO22+) is of great significance to the ecological environment. However, there is still a lack of efficient adsorption materials to remove UO22+ in wastewater economically. Because natural basswood has high porosity, natural hydrophilicity, and abundant surface functional groups, wood as a support material has a good application prospect in water treatment. In the present work, the amidoxime functional group (AO) is grafted to the hydroxyl group of the wood fiber (AO-wood). A carbon layer is formed on the surface of the basswood by heating, and some Ag nanoparticles with good optothermal effect are added to the wood tunnel (Ag-C-AO-wood). Ag-C-AO-wood is used for efficient wastewater treatment under light conditions. The adsorption kinetic of Ag-C-AO-wood is 4.6 h under one irradiation, which is 7 times faster than AO-wood. It has approached or even surpassed some traditional carbon materials with stirring. This method is expected to break the traditional stirring method. Ag-C-AO-wood can not only remove uranium up to 82% but also have a good removal efficiency (27%) on iodide ions. More importantly, due to basswood characteristics, it is possible to large-scale preparation and explore its potential application value in wastewater.


Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model.
To study the impact of aneuploid granulosa and stromal cells on folliculogenesis of small ovarian follicles from patients with mosaic Turner syndrome (TS) using a murine xenograft model. Laboratory study. University hospital. Ovarian cortical tissue was obtained by laparoscopic surgery from 18 patients with mosaic TS (aged 5-19 years) and 13 controls (aged 5-18 years). Part of each tissue fragment was used to karyotype ovarian cells in nongrafted tissue by fluorescence in situ hybridization. The remaining tissue was xenografted to severe combined immunodeficient mice for 5 months. Grafted tissue was analyzed for aneuploidy, and follicle density and morphology were determined. Expressions of proliferating cell nuclear antigen and anti-Müllerian hormone were investigated by immunohistochemistry. The impact of aneuploid granulosa and stromal cells on folliculogenesis. Fluorescence in situ hybridization of ovarian tissue before grafting was performed to determine the level of aneuploidy in stromal cells and oocytes and granulosa of small follicles. After xenografting, the level of aneuploidy of the newly formed layers of granulosa cells was again determined in secondary and antral follicles. Follicle density in ovarian tissue from patients with TS was significantly lower than in controls before grafting. Fluorescence in situ hybridization analysis confirmed that 101 of 104 oocytes from nongrafted tissue of patients with TS showed normal X chromosome content, whereas granulosa and stromal cells were mainly 45,X. Fragments from 12 patients with TS contained follicles at all stages after xenografting, including secondary and antral follicles. Follicle density in patients with TS and controls decreased significantly after grafting. Moreover, a shift from high to low proportions of 45,X granulosa cells was observed during folliculogenesis. Expression of proliferating cell nuclear antigen in follicles from patients with TS increased significantly during grafting. Secretion of anti-Müllerian hormone was impaired before grafting in peripubertal/postpubertal girls with TS, but recovered after grafting. Our study showed that small follicles from patients with mosaic TS undergoes folliculogenesis, despite the presence of aneuploid granulosa and stromal cells. Ovarian tissue cryopreservation could therefore be a valid option to preserve fertility in young patients with mosaic TS if sufficient numbers of follicles are present, thus preferably before the age of 12.


The risk of conversion in minimally invasive oncological abdominal surgery. Meta-analysis of randomized evidence comparing traditional laparoscopic versus robot-assisted techniques.
The objective of this study was to investigate the risk of conversion associated with conventional laparoscopic surgery (LAP) versus robot-assisted surgery (ROB) in patients undergoing abdominal oncological surgery. Possible differences between ROB and LAP on postoperative overall and major morbidity, operative time, and length of hospitalization were also assessed. We included randomized controlled trials of LAP versus ROB surgery in patients with abdominal malignancy. We searched PubMed, EMBASE, and the Central registries through September 2020. Risk of bias was estimated concerning randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases. A total of 1867 patients from 12 trials were included in this review. The rate of conversion was significantly higher for LAP than for ROB patients (10 trials, 1447 participants, p = 0.03, OR = 0.56 [0.33, 0.95]). There was a nonsignificant advantage of ROB over LAP on the rate of overall postoperative morbidity (12 trials, 1867 participants, p = 0.32, OR = 0.83) and major morbidity (7 trials, 792 participants, p = 0.87, OR= 0.93). ROB was also associated with prolonged operative time and abbreviated postoperative hospitalization as compared to LAP (p = 0.002, MD = 27.87, and p = 0.04, MD = -0.57, respectively). According to the available highest level of evidence, the application of ROB decreases the incidence of unplanned conversion into an open procedure as compared to standard LAP in the setting of oncological minimally invasive surgery.