The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin.

Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer's and Parkinson's diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.

Self-reported quality of life and hope in phase-I trial participants: An observational prospective cohort study.

For advanced cancer patients deliberating early clinical trial participation, adequate information about expected effect on quality of life (HRQoL) and hope, may support decision making. The aim was to assess the potential relation of HRQoL to eligibility for phase-I trial participation, and to observe the variations in patient-reported outcomes. Patients completed questionnaires at preconsent (n = 124), baseline (n = 96), and after first evaluation of a phase-I trial (n = 76). The Mann-Whitney U test was used to test differences between eligible and ineligible patients. Univariate logistic regression was performed for eligibility. Factorial repeated-measures ANOVA compared the outcomes of patients continuing vs. stopping participation after first evaluation over time. Eligibility is associated with significant better global health OR = 0.946, 95% CI [0.918, 0.975], p = 0.001, physical functioning OR = 0.959, 95% CI [0.933, 0.985], p = 0.002, role functioning OR = 0.974, 95% CI [0.957, 0.991] and better appetite OR = 1.114 95% CI [1.035, 1.192]. HRQoL outcomes like global health, social functioning and appetite decline in all patients and differ between patients continuing or having to end participation. Over time, hope and tenacity decline in all patients and coping strategies alter in patients stopping participation. Trial participation influences patient-reported outcomes. Global health may predict for eligibility and trial continuation. Informing patients could affect patients' decision making.

Live Birth from the Transfer of a Severely Fragmented Embryo Observed by Morphokinetics.

We report a live birth from a heavily fragmented embryo which continued cleavage to a fully expanded blastocyst. A 32-year-old patient underwent 2 IVF cycles without achieving pregnancy. In the first cycle, 2 embryos with fragmentation were transferred; in the second, all embryos were fragmented and no embryo transfer was performed. In a third cycle, 12 oocytes were retrieved and 11 of them were fertilized. On day 2, all 11 embryos started to unwind to fragments. By careful annotation, using the time-lapse EmbryoScope, we observed that one embryo continued division as expected, discarding all fragments aside. On day 5, this embryo showed promising annotation according to our lab model. The embryo was transferred into the uterus and resulted in the birth of a healthy baby at term. To our knowledge, this is the first case report assisted by EmbryoScope where a healthy baby was delivered from a fragmented embryo.

Apparent diffusion coefficient values obtained by unenhanced MRI predicts disease-specific survival in bladder cancer.

AIM: To assess the ability of apparent diffusion coefficient (ADC) measurements obtained by MRI to predict disease-specific survival (DSS) in patients with bladder cancer and compare it with established clinico-pathological prognostic factors. MATERIAL AND METHODS: The ethical review board approved this cross-sectional study. Patients with suspected bladder cancer receiving diagnostic 3 T diffusion-weighted imaging (DWI) of the bladder before transurethral resection of the bladder (TUR-B) or radical cystectomy were evaluated prospectively. Two independent radiologists measured ADC values in bladder cancer lesions in regions of interest. Associations between ADC values and pathological features with DSS were tested statistically. A combined model was established using artificial neuronal network (ANN) methodology. RESULTS: A total of 51 patients (median age 69 years, range 41-89 years) were included. Three patients were lost to follow-up, leaving 48 patients for survival analysis. Seven patients died during the 795 months studied. ADC showed significant potential to predict DSS (p<0.05). Except for grading, all pathological features as assessed by TUR-B could predict DSS (p<0.05, respectively). The combined ANN classifier showed the highest accuracy to predict DSS (0.889, 95% confidence interval: 0.732-1, p=0.001) compared to all single parameters. ADC was the second important predictor of the ANN. CONCLUSIONS: ADC measurements obtained by unenhanced MRI predicts DSS in bladder cancer patients. A combined classifier including ADC and clinico-pathological information showed high accuracy to identify patients at high risk for disease-related death.

Videolaryngoscopy for Physician-Based, Prehospital Emergency Intubation: A Prospective, Randomized, Multicenter Comparison of Different Blade Types Using A.P. Advance, C-MAC System, and KingVision.

BACKGROUND: Videolaryngoscopy is a valuable technique for endotracheal intubation. When used in the perioperative period, different videolaryngoscopes vary both in terms of technical use and intubation success rates. However, in the prehospital environment, the relative performance of different videolaryngoscopic systems is less well studied. METHODS: We conducted this prospective, randomized, multicenter study at 4 German prehospital emergency medicine centers. One hundred sixty-eight adult patients requiring prehospital emergency intubation were treated by an emergency physician and randomized to 1 of 3 portable videolaryngoscopes (A.P. Advance, C-MAC PM, and channeled blade KingVision) with different blade types. The primary outcome variable was overall intubation success and secondary outcomes included first-attempt intubation success, glottis visualization, and difficulty with handling the devices. P values for pairwise comparisons are corrected by the Bonferroni method for 3 tests (P[BF]). All presented P values are adjusted for center. RESULTS: Glottis visualization was comparable with all 3 devices. Overall intubation success for A.P. Advance, C-MAC, and KingVision was 96%, 97%, and 61%, respectively (overall: P < .001, A.P. Advance versus C-MAC: odds ratio [OR], 0.97, 95% confidence interval [CI], 0.13-7.42, P[BF] > 0.99; A.P. Advance versus KingVision: OR, 0.043, 95% CI, 0.0088-0.21, P[BF] < 0.001; C-MAC versus KingVision: OR, 0.043, 95% CI, 0.0088-0.21, P[BF] < 0.001). Intubation success on the first attempt with A.P. Advance, C-MAC, and KingVision was 86%, 85%, and 48%, respectively (overall: P < .001, A.P. Advance versus C-MAC: OR, 0.89, 95% CI, 0.31-2.53, P[BF] > 0.99; A.P. Advance versus KingVision: OR, 0.24, 95% CI, 0.055-0.38, P[BF] = 0.0054; C-MAC versus KingVision: OR, 0.21, 95% CI, 0.043-.34, P[BF] < 0.003). Direct laryngoscopy for successful intubation with the videolaryngoscopic device was necessary with the A.P. Advance in 5 patients, and with the C-MAC in 4 patients. In the KingVision group, 21 patients were intubated with an alternative device. CONCLUSIONS: During prehospital emergency endotracheal intubation performed by emergency physicians, success rates of 3 commercially available videolaryngoscopes A.P. Advance, C-MAC PM, and KingVision varied markedly. We also found that although any of the videolaryngoscopes provided an adequate view, actual intubation was more difficult with the channeled blade KingVision.

Understanding how coping strategies and quality of life maintain hope in patients deliberating phase I trial participation.

OBJECTIVE: This study aimed to understand how hope and motivation of patients considering phase I trial participation are affected by psychological factors such as coping strategies and locus of control (LoC) and general well-being as measured by the quality of life (QoL). METHODS: An exploratory cross-sectional study was performed in patients with incurable cancer (N = 135) referred to our phase I unit for the first time. Patients were potentially eligible for phase I trial participation and participated in our study while deliberating phase I trial participation. We used questionnaires on hope, motivation to participate, coping, LoC, and QoL. To investigate the nature and magnitude of the relationships between the scales, a structural equation modeling (SEM) was fitted to the data. RESULTS: Hope significantly predicted the motivation to participate in phase I trials. Predictors of hope were a combination of flexible and tenacious goal pursuit (both P < .01), internal LoC (P < .01), and QoL (P < .01). The SEM showed an exact fit to the data, using a null hypothesis significance test: chi-square (8) = 9.30, P = .32. CONCLUSIONS: Patients considering phase I trial participation seem to use a pact of tenacious and flexible coping and control to stay hopeful. Furthermore, hope and QoL positively affected each other. The psychological pact may promote an adaptation enabling them to adjust to difficult circumstances by unconsciously ignoring information, called dissonance reduction. This mechanism may impair their ability to provide a valid informed consent. We suggest including a systematic exploration of patients' social context and values before proposing a phase I trial.

MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.

The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.

Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors.

OBJECTIVE: To investigate utility and limitations of 3-Tesla diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiation of benign versus malignant renal lesions and renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS: Sixty patients with 71 renal lesions underwent 3 Tesla DW-MRI of the kidney before diagnostic tissue confirmation. The images were retrospectively evaluated blinded to histology. Single-shot echo-planar imaging was used as the DW imaging technique. Apparent diffusion coefficient (ADC) values were measured and compared with histopathological characteristics. RESULTS: There were 54 malignant and 17 benign lesions, 46 lesions being small renal masses ≤ 4 cm. Papillary RCC lesions had lower ADC values (p=0.029) than other RCC subtypes (clear cell or chromophobe). Diagnostic accuracy of DW-MRI for differentiation of papillary from non-papillary RCC was 70.3% resulting in a sensitivity and specificity of 64.3% (95% CI, 35.1-87.2) and 77.1 (95% CI, 59.9-89.6%). Accuracy increased to 83.7% in small renal masses (≤ 4 cm diameter) and sensitivity and specificity were 75.0% and 88.5%, respectively. The ADC values did not differ significantly between benign and malignant renal lesions (p=0.45). CONCLUSIONS: DW-MRI seems to distinguish between papillary and other subtypes of RCCs especially in small renal masses but could not differentiate between benign and malignant renal lesions. Therefore, the use of DW-MRI for preoperative differentiation of renal lesions is limited.

Gastric cancer in young patients.

AIM: The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. PATIENTS AND METHODS: Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. RESULTS: Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. CONCLUSION: Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance.

[Anaesthesia under unfavorable conditions - rescue helicopter]. / Anästhesie in anästhesiefeindlicher Umgebung - Tätigkeitsfeld Rettungshubschrauber.

Rescue helicopters are used for emergency care and transport of emergency patients. The dimension of the cabin is clearly limited. A transport is carried out under spatial narrowness and high noise levels. Acoustic alarms or noises caused by the patient are hardly to be perceived, so that the view at optical alarms is necessary. Environmental conditions affect the concentration on the patient. Rearrangement maneuvers represent the most critical phases. Always the whole apparative monitoring and respirator must be in the field of view of the emergency doctor, drugs to the care must be handy to be quickly administered, the quantity of oxygen has to be observed. Infusions and option of airway management are ready to set in advance. Standardized work with the aid of algorithms and knowledge of treatment recommendations and guidelines help to prevent errors. To optimize the care of emergency patients, special training courses for the crew of rescue helicopters are offered. A training simulator to practice different scenarios and the establishment of a CIRS system are recommended.

[Case Report: prehospital treatment on a major injured motorcycle driver]. / Kasuistik interaktiv: Verkehrsunfall - Präklinische Versorgung eines polytraumatisierten Motorradfahrers.

This case report describes the prehospital care of a 42-year-old person damaged by a severe motorcycle accident in a rural scene. The injured person was unconscious, one pupil was dilated and rib fractures were palpable. Purposeful therapy without delay was necessary. The prehospital therapy took 35 minutes in total. The time benefit by using a rescue helicopter is illustrated: time to initial treatment is minimized and duration of transport as well - direct transport to a trauma center is possible.

[Amputation of upper extremity: a case report - preclinical care of an 37 year old man]. / Kasuistik interaktiv: Amputation - Spektakuläre Verletzung, unkomplizierte Versorgung.

This case report describes the prehospital care of a person after an occupational accident. The amputation of whole extremities is rare and needs a standardized procedure: at first lifesaving procedures are necessary before saving the limb. The work at a conveyor belt resulted in taking of an arm. On the basis of this case report the prehospital management is discussed focalizing the complete treatment of the patient and his amputated extremity as well as the transport from the scene of accident to a suitable hospital.

[Case report: severe hypothermia in a newborn infant - challenges in preclinical emergency medicine]. / Kasuistik interaktiv: Neugeborenes mit schwerer Hypothermie - Eine notärztliche Herausforderung.

On the basis of a case report the prehospital management of a newborn child with deep accidental hypothermia (22oC) is discussed. The child was found in a garbage can. The continuous resuscitation during the transport into the clinic is done in an incubator and the child survives without neurologic damages. The used measures of the resuscitation are discussed on the basis of the therapy.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment.

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson chi(2) test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P = 0.022), deep myometrial invasion (P < 0.0001), and the presence of capillary space-like involvement (CSLI) (P = 0.003). Kaplan-Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P = 0.009) and a worse overall survival (log-rank test; P = 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P = 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P = 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

Imaging of renal leiomyomas.

BACKGROUND: Renal leiomyomas are rare benign tumors of the kidney which can be found at autopsy as small capsular nodules in about 5% of cases. The clinical incidence of such lesions is much smaller, and only case reports or small series have been reported in the imaging literature. PURPOSE: To describe the imaging characteristics observed in a series of eight patients with pathology-proven asymptomatic leiomyomas of the kidney. MATERIAL AND METHODS: We reviewed the imaging findings observed in eight patients with pathologically proven asymptomatic renal leiomyomas discovered during studies performed for reasons unrelated to the kidney. All patients had undergone computed tomography (CT), two ultrasonography, and one magnetic resonance imaging (MRI). RESULTS: Lesions ranged in size from 1.2 to 13 cm. Six were at the periphery of the kidney, compressed its outer surface, but did not cause disruption of the cortex; two involved the renal cortex. All had regular outer margins. A cleavage plane between the tumor and the kidney was revealed at CT and/or ultrasonography in three of the cases located at the periphery. At ultrasonography, leiomyomas appeared hypoechogenic. At CT, they were slightly hyperdense before contrast medium injection; all were hypodense to the renal cortex after contrast medium. Four were homogeneous, two were slightly heterogeneous, and the remaining two were frankly heterogeneous. The lesion studied by MRI, which was homogeneous at the postcontrast CT study, had a heterogeneous structure on both T1- and T2-weighted images, with internal areas of hypointensity on T1. CONCLUSION: There are some imaging findings that can help to suggest the diagnosis of renal leiomyomas. First, their density: all tumors examined before contrast were hyperdense to the kidney, with density similar to that of muscles, and all had lower enhancement than the adjacent renal parenchyma. Second, the location and margins of the tumors: most were peripheral, without involvement of the renal cortex and with well-defined margins. Although not pathognomonic for a renal leiomyoma, the combination of these findings should include leiomyoma in the list of differential diagnoses.

Does hysteroscopy affect prognosis in apparent early-stage endometrial cancer?

The objective of the study was to compare the outcome measures of patients with endometrial adenocarcinoma diagnosed by endometrial biopsy, uterine curettage, or hysteroscopy. Medical records of 392 women diagnosed with apparent early-stage endometrial adenocarcinoma were reviewed. Data concerning the mode of diagnosis, histologic type and grade, surgical stage, peritoneal washings and lymph nodes status, and patient's outcome were retrieved. During the study period, 99 (25.3%) cases were diagnosed by endometrial biopsy, 193 (49.2%) by uterine curettage, and 100 (25.5%) by hysteroscopy. There were 347 (88.5%) cases of endometrioid adenocarcinoma and 45 (11.5%) of poor histologic types, including serous papillary, clear cell, and small cell cancer. Three hundred and sixteen (80.6%) patients had stage I disease, 8 (2.0%) stage II, and 68 (17.4%) stage III. Peritoneal cytology was positive in only one case. Recurrent disease occurred in 6.9% patients, of which 50% had local recurrence and 50% had distant. Recurrent disease was found in 15.2% patients diagnosed by endometrial biopsy, in 4.7% where uterine curettage was used, and in 5% when hysteroscopy was applied. No statistically significant difference in the survival rate between the different diagnostic methods applied was found, although a higher recurrence rate was noted following endometrial biopsy. After a median follow-up time of 25 months for patients undergoing hysteroscopy, there was no difference in recurrence rates and/or overall survival compared to other diagnostic procedures implying that hysteroscopy can be safely used in the diagnosis of endometrial cancer.

[Case report: prehospital therapy of the severely burned patient]. / Kasuistik interaktiv: grossflächige Verbrühung - Das Einmaleins der Brandverletzten-Versorgung.

On the basis of a case report the prehospital management of severely burned patients is discussed. The prevention of hypovolemia, hypothermia or hypoxemia are the primary targets. It is necessary to estimate the burn size and depth. The burn shock fluid resuscitation, prevention of hypothermia, pain- and airway management are described as well as the transport from the scene of accident to a proximal emergency unit or to a specialized burn intensive care unit.

[Case report: severe polytrauma after traffic accident]. / Kasuistik interaktiv: Schwerer Verkehrsunfall--Eingeklemmt, und die Zeit läuft.

This case report describes the prehospital care of a person with severe polytrauma due to being jammed in a vehicle in a traffic accident. After understanding the forces involved in causing the trauma, the therapy of impaired vital functions is demonstrated with particular regard to time management. Use of a rescue helicopter allowed for minimizing the delay to initial treatment as well as the duration of transport.

Elevated platelet vesicular monoamine transporter 2 in former heroin addicts maintained on methadone.

The brain vesicular monoamine transporter (VMAT2) is essential for neuronal monoamine storage and regulation of monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Opioids induce increase of dopamine release in limbic structures. In the present study we assessed the VMAT2 pharmacodynamic characteristics using high affinity [(3)H]dihydrotetrabenazine (TBZOH) binding to platelets of former male heroin addicts maintained on methadone (n = 12) compared to age-matched healthy controls (n = 13). A significant increase (19%, p < 0.05) in platelet VMAT2 density (Bmax) was observed in the methadone treated patients compared to controls. There was no significant difference in the affinity of [(3)H]TBZOH to its platelet binding site. The increased VMAT2 density may reflect a compensatory attempt to prevent vesicular depletion due to chronic methadone exposure.