1st Blocks Research Articles

Shell-by-Shell functionalized nanoparticles as radiosensitizers and radioprotectors in radiation therapy of cancer cells and tumor spheroids

Shell-by-Shell (SbS)-functionalized NPs can be tailor-made by combining a metal oxide NP core of choice with any desired phosphonic acids and amphiphiles as 1st or 2nd ligand shell building blocks. The complementary composition of such highly hierarchical structures makes them interesting candidates for various biomedical applications, as certain active ingredients can be incorporated into the structure. Here, we used TiO2 and CoFe2O4 NPs as drug delivery tools and coated them with a hexadecylphosphonic acid and with hexadecyl ammonium phenolates (caffeate, p-coumarate, ferulate), that possess anticancer as well as antioxidant properties. These architectures were then incubated in 2D and 3D cell cultures of non-tumorigenic and tumorigenic breast cells and irradiated to study their anticancer effect. It was found that both, the functionalized TiO2 and CoFe2O4 NPs acted as strong protective agents in non-tumorigenic spheroids. In contrast, the functionalized CoFe2O4 NPs induce a higher damage in irradiated tumor spheroids compared to the functionalized TiO2 NPs. CoFe3O4 NPs act additionally as radiosensitizing agents to the tumor spheroids. The radio-enhancement of the CoFe2O4 NPs is due to the generation of highly toxic hydroxyl radicals during X-ray irradiation. The irradiation exposed the CoFe2O4 surface, releasing the anticancer drugs into the cytoplasm and making the surface Co2+ ions accessible. These surface ions catalyze the Fenton reaction. This combination of radiosensitizer and anticancer drug delivery proved to be a very effective nanotherapeutic in 2D and 3D cell cultures of breast cancer cells.

Faculty development program assists the new faculty in constructing high-quality short answer questions; a quasi-experimental study.

Faculty development programs (FD) prepare the faculty for their educational role and career tasks. We aimed to evaluate the effectiveness of FDP in advancing the quality of short-answer questions (SAQs). This was a quasi-experimental study, comprising 37 new faculty. The SAQs were examined on psychometric analysis and Bloom’s cognitive levels for the two educational blocks of 1st medical year (i.e. Musculoskeletal (MSK) and Renal blocks). We found substantial improvement in the discrimination index values of SAQs prepared after the workshop (p = 0.04). A higher number of SAQs with moderate difficulty and higher discrimination were also observed. Flaws within the post-workshop questions were reduced (3.0%) when compared with pre-workshop (12.5%). The major incline was also reported within Bloom’s cognitive levels when pre-workshop K2 questions (30%) were compared with post-workshop (45.5%) with a p-value = 0.05. The SAQs constructed by the faculty member without participating in FDP are generally of unsatisfactory quality. After the FDP the assessment items of two blocks improved for various parameters of student assessment. The current study advocates that newly joined faculty shall be provided with the FDP to be guided, trained and supported for improving the quality of assessment through SAQs items writing.

Feasibility of a combined mobile-health electrocardiographic and rapid diagnostic test screening for Chagas-related cardiac alterations

Abstract Background Chronic Chagas cardiomyopathy (CChC) is the most common cause of death related to Chagas disease (CD), and it develops in 20–30% of infected individuals. However, access to both CD testing and basic cardiac care is often limited in rural deprived areas, hyperendemic for CD. Purpose To assess the feasibility of a combined mobile-health (m-Health) electrocardiographic (ECG) and rapid diagnostic test (RDT) screening for Chagas-related cardiac alterations in a remote rural village of the Bolivian Chaco, where a high prevalence of CChC is expected. Methods A representative sample of 140 healthy volunteers were consecutively enrolled in a rural Bolivian Community in February 2019. Demographic and clinical data were recorded through a standardized questionnaire. All patients performed an ECG by D-Heart, a validated low-cost hospital grade 8 and 12 lead smartphone portable ECG, and a serologic testing by Chagas Stat-Pak® (CSP). RDTs were read locally while ECGs were sent to a Cardiology clinic which transmitted reports within 24 hours from recording. Results Among 140 people (54 men, median age of 38 [23–54] years), 98 (70%, 95% CI 62.4–77.6) were positive for T. cruzi infection with CSP, with a linear, age-dependent, increasing trend (p<0.001). Overall, 25 individuals (18%) showed ECG abnormalities, compatible with CD. Prevalence of ECG abnormalities was significantly higher in T. cruzi infected individuals (22 vs 7%, p=0.032). None of the study participants had performed an ECG test prior to enrolment. ECG abnormalities included Bundle Branch Blocks (n=8), 1st Degree Atrioventricular blocks (n=3), rhythm disturbances (n=5), pathologic Q waves (n=2), fragmented QRS (n=5) and low QRS voltage (n=2). Twenty-two patients with a positive CSP testing and possible CD-related ECG abnormalities were recalled from Camiri Community and referred to Gutierrez Hospital for chest X-ray and treatment initiation. At multivariate analysis, positive CSP results (OR 4.75, 95% CI 1.08–20.96, p=0.039) and smoking habit (OR 4.20, 95% CI 1.18–14.92, p=0.027) were confirmed as independent predictors of ECG abnormalities. For 6-day screening for a community of 150 inhabitants, the overall start-up amount was projected to 4.82$/patient and to 8.23$/patient when operative costs (i.e. on-site nurse and healthcare assistant with remote physician on call) were included. Conclusions Combined D-Heart® ECG and RDTs screening proved a reliable and effective low-cost strategy to identify patients at high risk of disease and in need of further cardiologic assessment, in a rural, highly endemic environments of the Bolivian Chaco. Onsite and m-Health programmes should be encouraged to support early diagnosis of CD and CChC and provide access to targeted therapy to maximize treatment benefits prior to advanced cardiac involvement. Funding Acknowledgement Type of funding source: None

Inverse Correlation between Stress and Adaptive Coping in Medical Students

BACKGROUND: Medical students in their academic years are generally under stress but very few studies revealed the relationship between the stress and how the students manage to adapt these stressful conditions.
 AIM: The aim of the study was to investigate the levels of stress and their adaptive coping in the 1st 3 years medical students and also to determine the factors associated with adaptive coping strategies.
 METHODS: This is a descriptive cross-sectional study conducted on 441 medical students of Qassim University from September-October 2019. First 3 years medical students were randomly selected and their stress levels or adaptive coping strategies were determined by general health questionnaire (GHQ-12) and strategies coping mechanisms (SCM), respectively. The 5-points Likert scale was used for scoring and the data obtained were further validated by DASS and Brief COPE scales.
 RESULTS: Out of 441 medical students, 39.2% agreed to participate. The data showed that the level of stress among students was highest during their 1st year academic blocks, followed by 2nd and 3rd year students. Interesting, the adaptive coping among them was found highest during the academic blocks of 3rd year students, followed by the 2nd and 1st year students. Importantly, female students showed better adaptation against stress. Students living with their parents avoided stress in better ways as compared to those who were living alone.
 CONCLUSION: This is the first study that shows an inverse correlation between the stress and adaptive coping in medical students of Qassim University. The data concluded that adaptation of stress in the 3rd-year students was the highest followed by 2nd and 1st year medical students. Moreover, female students adapted well against stress and students living alone showed worse adaptation of stress.

Design and application examples of CMOS fractional-order differentiators and integrators

Reduced complexity CMOS fractional-order differentiator and integrator building blocks are introduced in this work, based on 2nd-order integer-order transfer function approximations. These blocks are then used for implementing fractional-order filters as well as a Leaky-Integrate-and-Fire Mihalas-Niebur neuron model. Cascading 1st and 2nd-order blocks to obtain 5th-order integer-order transfer functions, improved bandwidth of approximation accuracy is achieved. Furthermore, the realization of fractional-order capacitor and inductor emulators is demonstrated.

The maturation of auditory responses in infants and young children: a cross-sectional study from 6 to 59 months.

Background: An understanding of the maturation of auditory cortex responses in typically developing infants and toddlers is needed to later identify auditory processing abnormalities in infants at risk for neurodevelopmental disorders. The availability of infant and young child magnetoencephalography (MEG) systems may now provide near optimal assessment of left and right hemisphere auditory neuromagnetic responses in young populations. To assess the performance of a novel whole-head infant MEG system, a cross-sectional study examined the maturation of left and right auditory cortex responses in children 6- to 59-months of age.Methods: Blocks of 1000 Hz (1st and 3rd blocks) and 500 Hz tones (2nd block) were presented while MEG data were recorded using an infant/young child biomagnetometer (Artemis 123). Data were obtained from 29 children (11 males; 6- to 59-months). Latency measures were obtained for the first positive-to-negative evoked response waveform complex in each hemisphere. Latency and age associations as well as frequency and hemisphere latency differences were examined. For the 1000 Hz tone, measures of reliability were computed.Results: For the first response—a response with a “P2m” topography—latencies decreased as a function of age. For the second response—a response with a “N2m” topography—no N2m latency and age relationships were observed. A main effect of tone frequency showed earlier P2m responses for 1st 1000 Hz (150 ms) and 2nd 1000 Hz (148 ms) vs. 500 Hz tones (162 ms). A significant main effect of hemisphere showed earlier N2m responses for 2nd 1000 Hz (226 ms) vs. 1st 1000 Hz (241 ms) vs. 500 Hz tones (265 ms). P2m and N2m interclass correlation coefficient latency findings were as follows: left P2m (0.72, p < 0.001), right P2m (0.84, p < 0.001), left N2m (0.77, p < 0.001), and right N2m (0.77,p < 0.01).Conclusions: Findings of strong age and latency associations, sensitivity to tone frequency, and good test-retest reliability support the viability of longitudinal infant MEG studies that include younger as well as older participants as well as studies examining auditory processing abnormalities in infants at risk for neurodevelopmental disorders.

Modification of motor cortex excitability during muscle relaxation in motor learning

We postulated that gradual muscle relaxation during motor learning would dynamically change activity in the primary motor cortex (M1) and modify short-interval intracortical inhibition (SICI). Thus, we compared changes in M1 excitability both pre and post motor learning during gradual muscle relaxation.Thirteen healthy participants were asked to gradually relax their muscles from an isometric right wrist extension (30% maximum voluntary contraction; MVC) using a tracking task for motor learning. Single or paired transcranial magnetic stimulation (TMS) was applied at either 20% or 80% of the downward force output during muscle release from 30% MVC, and we compared the effects of motor learning immediately after the 1st and 10th blocks. Motor-evoked potentials (MEPs) from the extensor and flexor carpi radialis (ECR and FCR) were then measured and compared to evaluate their relationship before and after motor learning. In both muscles and each downward force output, motor cortex excitability during muscle relaxation was significantly increased following motor learning. In the ECR, the SICI in the 10th block was significantly increased during the 80% waveform decline compared to the SICI in the 1st block. In the FCR, the SICI also exhibited a greater inhibitory effect when muscle relaxation was terminated following motor learning. During motor training, acquisition of the ability to control muscle relaxation increased the SICI in both the ECR and FCR during motor termination. This finding aids in our understanding of the cortical mechanisms that underlie muscle relaxation during motor learning.

Implicit sequence learning in people with Parkinson's disease.

Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these tasks. The present study used an implicit sequence learning task with a reduced motor component, the Triplets Learning Task (TLT). People with PD and age- and education-matched healthy older adults completed three sessions (each consisting of 10 blocks of 50 trials) of the TLT. Results revealed that the PD group was able to learn the sequence, however, when learning was examined using a Half Blocks analysis (Nemeth et al., 2013), which compared learning in the 1st 25/50 trials of all blocks to that in the 2nd 25/50 trials, the PD group showed significantly less learning than Controls in the 2nd Half Blocks, but not in the 1st. Nemeth et al. (2013) hypothesized that the 1st Half Blocks involve recall and reactivation of the sequence learned, thus reflecting hippocampal-dependent learning, while the 2nd Half Blocks involve proceduralized behavior of learned sequences, reflecting striatal-based learning. The present results suggest that the PD group had intact hippocampal-dependent implicit sequence learning, but impaired striatal-dependent learning. Thus, sequencing deficits in PD are likely due to striatal impairments, but other brain systems, such as the hippocampus, may be able to partially compensate for striatal decline to improve performance.

Long-term Outcome of Trigeminal Nerve Block with Alcohol for the Treatment of Trigeminal Neuralgia

Background: Recently trigeminal nerve block with alcohol (TnbA) for the treatment of trigeminal neuralgia (TN) has come to be known as a procedure with a short-term effect and high complications. There has been none of report about long-term outcome of TnbA for TN. The objective of this prospective study for the long-term results of TnbA was to analyse the pain free duration and complication after the administration of blocks and compare them in the first block and subsequent blocks. Methods: From March 1996 to May 2005, 304 consecutive patients with primary trigeminal neuralgia were treated with TnbA including supraorbital nerve block, infraorbital nerve block, maxillary nerve (V2) block, mandibular nerve (V3) block, and V2 and V3 at the same time and were prospectively followed up every two months for 10 years. Results: The mean value of pain free duation of 1st, 2nd and 3rd TnbA were 43, 38 and 48 months, respectively using Kaplan-Meier analysis. The probability of pain recurrence in 1 and 3 years after the 1st, 2nd and 3rd blocks were 25%, 25%, 20% and 53%, 54%, 34%, respectively. The pain free durations of first and subsequent blocks were not statistically different. Complications were reported at 36 (11.8%), 5 (4.2%), and 0 in 1st, 2nd and 3rd blocks. Conclusions: TnbA showed the relatively long duration of pain free and low incidence of complications. Repeated TnbA has pain free duration as long as the 1st block and less complications as well. TnbA is a valuable treatment of TN as a percutaneous procedure. (Korean J Pain 2006; 19: 45-50)

Effects of Combination of a Transforaminal Nerve Root Block and an Epidural Steroid Injection for Chronic Radiating Pain

Methods: Thirty patients who suffered from chronic radiating pain that resistant conservative treatments including epidural steroid injection (ESI) were enrolled. Following a transforaminal nerve root block under fluoroscopic visualization, an ESI was administered at the level of the intervertebral space showing an obstacle to cephalad epidural spread of the dye injected during a transforaminal nerve root block. Twenty to forty mg of triamcinolone with 0.5% lidocaine was injected in divided doses. The patients received these nerve blocks at intervals of 1-2 weeks until the patients were satisfied with the results. If the pain reappeared, repeated blocks were administered at intervals of 2 months. Treatment results were evaluated twice using a pain relief scale and categorized as excellent, good, fair, or poor. Results: Pain improvements of more than 50% of the initial pain intensity, graded excellent or good, were observed in 66.7% at 1 week after the 1st blocks and 73.3% at 3 months after the final blocks. Conclusions: These findings suggest that a combination of a transforaminal nerve root block and ESI is an effective procedure for radiating pain not responding to ESI. However, comparative prospective studies to determine the effects of this combination therapy versus classical transforaminal injections may be mandatory.

Synthesis method for testable electrical networks using 1st order building blocks

This work presents a method for synthesizing testable continuous-time linear time-invariant electrical networks using 1st order blocks for the implementation of analog linear circuits. A functional–structural fault model for the block, and a fault dictionary are proposed together with a simple set of test vectors. The method allows, also, the fault grade evaluation for the modeled faults. The results obtained from the two application examples have shown the suitability of the approach as a design for test method for analog circuits.

Habituation of P300 from auditory stimuli

In a series of three experiments, the habituation effects on the P300 or P3 event-related brain potential (ERP) elicited with a simple auditory stimulus discrimination task were evaluated. In Experiment 1, possible changes in the P3 for the first 15 individual target stimulus trials were investigated. Neither the component amplitude or latency changed across trials when the target probability was 10%, 30%, or 50%. In Experiment 2, a target probability of 20% was employed, with 10 blocks of 20 target trials that were collected continuously. P3 amplitude declined significantly between the 1st and 10th trial blocks, with no decrements in target-detection performance observed. P3 latency tended to increase with repeated presentations. Experiment 3 was similar to Experiment 2, but the pitch of the target stimulus was changed after the 9th trial block. P3 amplitude again declined between the 1st and 9th trial blocks, but it increased significantly on the 10th block when the target stimulus changed, thereby demonstrating dishabituation. A second decrease in amplitude occurred by the 15th trial block. P3 latency tended to increase with repeated presentations but decreased with the stimulus change. The P3 component elicited with an active discrimination task and auditory stimuli does habituate after a sufficient number of trials have been presented. The implications of these results for the theoretical interpretation of the P3 are discussed.

An examination of the semantic adjustment hypothesis of contrast effects in loudness judgments

Subjects were presented a series of soft tones for loudness judgments using a category rating scale. After several blocks of soft tones, sets of loud tones were introduced to be presented along with the soft tones. This shift in the level of the tones to be judged was employed to examine any contrast effects (shifts in judgment) for the soft tones in comparison with earlier judgments. The loud series was presented only on the 1st postshift trial block, or on the 1st and 5th such trial blocks, or on the 1st, 5th, and 9th blocks, or on all 12 postshift trial blocks. The form of the contrast effects obtained across these groups was examined for its support of Steven’s (1958) semantic adjustment hypothesis of category judgments.