Notes

Facile Combination associated with Chiral Arylamines, Alkylamines and also Amides through Enantioselective NiH-Catalyzed Hydroamination.
SIPA1, a GTPase activating protein that negatively regulates Ras-related protein (Rap), is a potential modulator of tumor metastasis and recurrence. In this study, we first showed that SIPA1 facilitated the stemness features of breast cancer cells, such as of tumorsphere formation capability and the expression of stemness marker CD44. In addition, SIPA1 promoted the expression of four stemness-associated transcription factors through increasing the expression of SMAD2 and SMAD3 in vitro and in vivo. The stemness features were abolished by blocking the phosphorylation of SMAD3 with its specific inhibitor SIS3. Furthermore, SIPA1 decreased the breast cancer cell sensitivity to chemotherapy drugs. This effect was, however, competitively reversed by blocking the SMAD3 phosphorylation by SIS3 treatment in breast cancer cells. Taken together, SIPA1 promotes and sustains the stemness of breast cancer cells and their resistance to chemotherapy by increasing the expression of SMAD2 and SMAD3, and blocking SMAD3 phosphorylation could suppress the cancer cell stemness and increase the sensitivity to chemotherapy in breast cancer cells expressing a high level of SIPA1.To explore the effect of glutamine (Gln) on the growth performance, digestive enzyme activity, absorption function and mRNA expression of intestinal transporters in heat-stressed chickens, 540 21-day-old Arbor Acres broilers were randomly assigned to a control group (no stress, NS), Gln group (Chickens were administered 0.5% and 1.0% Gln, respectively), heat stress group (HT), and Gln + HT group (Chickens were administered 0.5% and 1.0% Gln, respectively). The chickens in the HT and Gln + HT groups were reared under HT (36 ± 1 °C for 10 h/d and 22 ± 1 °C for 14 h/d), for 21 days. In contrast to the NS group, heat stress caused a reduction in the body weight gain (BWG); feed intake (FI); activity of trypsin, lipase, alkaline phosphatases, Ca2+ and Mg2+ adenosine triphosphatases, and Na+-K+-ATPase; and content of glutathione and d-xylose (P less then 0.05) in the other groups. In addition, compared to the FG and expression levels in the NS group, the heat stress increased the feed intakebody weight gain (FG) and mRNA expression levels of SGLT1, CaBP-D28k, and L-GSBP (P less then 0.05). Furthermore, HT-challenged birds were pretreated with Gln, the BWG; FI; activity of trypsin, lipase, alkaline phosphatase, Ca2+ and Mg2+ adenosine triphosphatases, and Na+-K+-ATPase; and content of glutathione and d-xylose (P less then 0.05) were dramatically increased, but it decreased the FG and mRNA expression levels of SGLT1, CaBP-D28k, and L-GSBP (P less then 0.05) in the HT group. In summary, Gln can effectively improve growth performance and may promote digestion and absorption in the gastrointestinal tract by mediating the mRNA expression level of nutrient transporters and Gln metabolism in heat-stressed broilers.
We retrospectively analyzed the seizure characteristics, EEG pattern, treatment, and outcome in a series of patients with self-limited epilepsy with centrotemporal spikes (SLECTS) who presented with unusual clinical manifestations.

A retrospective, descriptive, multicenter study was conducted evaluating 46 patients with SLECTS who had seizures with an unusual semiology. We collected data from patients with SLECTS seen at eight Argentine centers between April 1998 and April 2018.

Thirteen patients (28.2 %) had seizures with affective symptoms characterized by sudden fright and autonomic disturbances and mild impairment of consciousness. Eleven patients (24.8 %) had frequent seizures characterized by unilateral facial sensorimotor symptoms, oropharyngolaryngeal manifestations, and speech arrest with sialorrhea only when awake. Seven patients (15.3 %) started with opercular epileptic status with unilateral or bilateral clonic seizures of the mouth with speech arrest and sialorrhea when awake and during sleep. Seven patients (15.3 %) had postictal Todd's paralysis after unilateral clonic seizures with facial and limb movements lasting between 60 min and 130 min. Six patients (13 %) had negative myoclonus, two in a unilateral upper limb, two in a unilateral lower limb, and the remaining two patients had frequent falls. One patient (2.1 %) had focal sensorimotor seizures characterized by unilateral numbness in the cheeks and one upper limb, additional to unilateral facial clonic seizures, speech arrest, and sialorrhea. The remaining patient (2.1 %) had sporadic focal tonic-dystonic seizures in the left upper limb only during sleep.

In our study, we found evidence of the existence of unusual clinical cases of SLECTS with typical EEG patterns and an excellent prognosis.
In our study, we found evidence of the existence of unusual clinical cases of SLECTS with typical EEG patterns and an excellent prognosis.
Ictal Single Photon Emission Computed Tomography (iSPECT) is one of the established tools utilized in the presurgical evaluation of patients with drug-resistant epilepsy (DRE). Timely isotope injection for an iSPECT is critical for optimal yield but poses logistical challenges when done manually. We aim to evaluate the added value of automatic iSPECT injectors (ASIs) in overcoming such challenges.

We retrospectively reviewed all cases admitted to the University of Pittsburgh Medical Center (UPMC) Epilepsy Monitoring Unit from Jan 1, 2010, through Dec 31, 2016, who underwent an iSPECT. We compared the manually injected iSPECTs with those performed with ASIs.

A total of 123 iSPECTs were reviewed. The manually injected iSPECT group consisted of 35 patients (median age, 35 years; and 19 males). The automatically injected iSPECT group consisted of 88 patients (median age, 36 years; and 46 males). The two groups were comparable in age, gender, epilepsy treatment, focal features on neuropsychological testing (tions, provides a safer injection option for the EMU staff, and leads to a significant improvement in the number of successfully localizing iSPECTs.Perampanel is a new antiepileptic drug with unique mechanism of action - antagonism of AMPA receptors. Its action in immature animals is not yet sufficiently known therefore we started to study anticonvulsant action of perampanel pretreatment (1-20 mg/kg i.p.) against seizures elicited by pentylenetetrazol. Three age groups of rats were examined - 12, 18 and 25 days old. Perampanel selectively suppressed the tonic phase of generalized seizures in the two younger groups and whole tonic-clonic seizures in the 25-day-old group. It exhibited also an anticonvulsant action against minimal clonic seizures present in control 18- and 25-day-old rats. Perampanel is an effective anticonvulsant drug even at very early stages of brain development.The analysis of the immune gene expression was performed in Zebu × Holstein calves with resistant and susceptible phenotypes naturally infected with Cooperia punctata. Fourteen calves of 4 months old were grazed for 11 weeks under a tropical climate. The parasitic infection showed an average epg value of 1055 ± 1155 and an IgG optical density of 0.814 ± 0.0.037 with statistic differences among the different weeks (p 0.05). High variation in epg value was observed, between 7 ± 7.14 and 4657 ± 1886, and, based on these differences; the infected hosts were classified as five resistant calves with epg ≤ 200 and nine susceptible calves with epg ≥ 300. Moreover, IgG levels displayed statistical differences between resistance and susceptible calves to C. punctata infection. The immune gene expression was analysed in three resistant and susceptible calves, respectively. Nine cytokine genes and the FCεR1A receptor were analysed at the 3rd and 11th weeks post-infection. In the first period upregulation was found, from 2.19- to 9.45-fold, (p  less then  0.05) for IL-2, -5, - 6, -10, TGF-β and FCεR1A in the resistant group; the expression was decreased at the 11th week with low level of IgG. In contrast, downregulation for susceptible calves was found for nine immune genes and upregulation for INF-γ in both periods together with increased IgG levels. In conclusion, immune gene expression was regulated at the begging infection of C. punctata in resistant grazing calves. In contrast, suppression of important genes was involved in calves susceptible to C. punctata.
B-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11, also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients.

Patients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. this website Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del.

In total, 152 Chinese Han NSCLC patients-nt prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients.

BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.
BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.The search for victims of World War Two (WWII) and the immediate aftermath period (postwar) in Croatia started together with the search for Homeland War victims in 1991. It continued through years, most often sporadically and in a non-homogenous way. It was just with the adoption of the Law on Research, Arrangement and Maintenance of Military Cemeteries, Cemeteries of Victims of WWII and Postwar Period in 2013 that the search became more structured and gained a formal governmental body responsible for the organization and supervision of the activities related to it. It was then that the well-established model of searching for Homeland War victims, based on many years of field work and research, started to be implemented in the search and analysis of WWII/postwar victims. The model represents a continuously growing and developing project which encompasses a wide variety of steps and procedures, from the investigation of alleged burial locations to the analysis and reburial of recovered mortal remains. From its implementation in 2016, it allowed the successful investigation of 1300 alleged burial locations, 484 field surveys, 42 exhumations and the recovery of remains of more than 1600 individuals. Besides, care for military cemeteries, marking of mass burial sites and arranging of international treaties are conducted in order to guarantee proper handling, relocation and repatriation of all those that perished during WWII and the postwar period.
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