Patient-reported cognitive impairments and objective neuropsychological deficits in young sarcoma patients undergoing chemotherapy and its comparison to healthy controls: A tertiary health care study from India.

The study aims to investigate the patient-reported cognitive deficits and objective neuropsychological functions in younger adult (YA) sarcoma patients (16-40 years of age). Ninety patients and 30 age-matched healthy controls from a single tertiary healthcare hospital, were recruited into four groups: Pre-chemotherapy (Pre Cx), During chemotherapy (During Cx), Post-chemotherapy (Post Cx) and Controls. Neurocognitive functions were assessed subjectively using FACT-Cog v3 questionnaire; objectively using ACE-III and neuropsychological tests (NPT). FACT-Cog scores of During Cx (P = .041) and Post Cx (P = .008) groups were significantly lower than Pre Cx group. ACE-III scores of During Cx (P = .048) and Post Cx (P = .043) groups were lower as compared to Pre Cx group. In addition, reaction times and accuracies of the NPT (Flanker's, Sternberg's and Emotional Stroop tests) were worse (P < .05) in During Cx and Post Cx groups as compared to either Pre Cx or control groups. In the Post Cx group, the dose of chemotherapy showed significant negative correlation with the Sternberg reaction time (P = .040) as well as the scores of language (P = .047), and attention (P = .044) domains of ACE-III. Observations demonstrate that cancer/chemotherapy-related neurocognitive deficits fail to improve even after cessation of treatment, and high dosage of chemotherapy used, could be an underlying factor. This emphasizes the need for developing 'model of care' in these patients for monitoring the side effects, and possible titration in the therapeutic regimen for sarcoma in YA.

Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

A Clinical Conundrum with Diagnostic and Therapeutic Challenge: a Tale of Two Disorders in One Case.

Living organisms are exposed to exogenous and endogenous agents that affect genomic integrity by creating DNA double strand breaks (DSBs). These breaks are repaired by DNA repair proteins to maintain homeostasis. Defects in DNA repair pathways also affect lymphocyte development and maturation, as DSB sites are critical intermediates for rearrangements required for V(D)J recombination. Recent classifications for inborn errors of immunity (IEIs) have listed DNA repair defect genes in a separate group, which suggests the importance of these genes for adaptive and innate immunity. We report an interesting case of a young female (index P1) with mutations in two different genes, DCLRE1C and FANCA, involved in DNA repair pathways. She presented with clinical manifestations attributed to both defects. With the advent of NGS, more than one defect is increasingly identified in patients with IEIs. Familial segregation studies and appropriate functional assays help ascertain the pathogenicity of these mutations and provide appropriate management and genetic counseling.

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India.

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

Frontal activation as a key for deciphering context congruity and valence during visual perception: An electrical neuroimaging study.

The object-context associations and the valence are two important stimulus attributes that influence visual perception. The current study investigates the neural sources associated with schema congruent and incongruent object-context associations within positive, negative, and neutral valence during an intermittent binocular rivalry task with simultaneous high-density EEG recording. Cortical sourceswere calculated using the sLORETA algorithm in 150 ms after stimulus onset (Stim + 150) and 400 ms before response (Resp-400) time windows. No significant difference in source activity was found between congruent and incongruent associations in any of the valence categories in the Stim + 150 ms window indicating that immediately after stimulus presentation the basic visual processing remains the same for both. In the Resp-400 ms window, different frontal regions showed higher activity for incongruent associations with different valence such as the superior frontal gyrus showed significantly higher activations for negative while the middle and medial frontal gyrus showed higher activations for neutral and finally, the inferior frontal gyrus showed higher activations for positive valence. Besides replicating the previous knowledge of frontal activations in response to context congruity, the current study provides further evidence for the sensitivity of the frontal lobe to the valence associated with the incongruent stimuli.

Electroencephalography-based cortical sources of working memory in the subjects with opioid addiction: A pilot study.

Background & objectives: Working memory impairments in the subjects of opioid addiction may stem from an aberrant cortical activity in the executive areas, and may help in early identification of individuals with addictive tendencies and may also be used as a neurofeedback mechanism in adjunct to the existing therapeutics. Methods: Electrical neuroimaging via 128-channel electroencephalography (EEG) recording was done in 15 male subjects with opioid addiction (29.45±5.6 yr) during the performance of Sternberg Working Memory Task. EEG data were acquired and analyzed for cortical sources during task as compared to resting (baseline) condition. Results: Working memory deficits were manifested as decrease in accuracy percentage in the subjects with opioid addiction, while no significant difference was seen in reaction time, on comparison with laboratory-acquired matched controls. Standardized low-resolution brain electromagnetic tomography (sLORETA)-based EEG source analysis revealed higher cortical activity in the anterior cingulate cortex, inferior, middle and superior temporal gyri, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule and precuneus, whereas significant lower activity was seen in superior and middle frontal gyri, parietal lobule, cingulate cortex and pre- and postcentral gyri when the task was compared to baseline in the subjects with opioid addiction. Further, a negative correlation was seen between the accuracy of task performance and activation ratio for the significant gyri in the subjects with opioid addiction. Interpretation & conclusions: EEG cortical sources revealed the failure of deactivation of default-mode network (DMN) during the task amongst the subjects with opioid addiction. In addition, there was a decrease in the executive function areas in the subjects with opioid addiction. This lack of sufficiently active executive network and persistence of DMN during the task (as compared to baseline) may potentially form the basis of functional impairments in the subjects with opioid addiction.

Brain Networks Communicate Through Theta Oscillations to Encode High Load in a Visuospatial Working Memory Task: An EEG Connectivity Study.

The encoding of visuospatial information is the foremost and indispensable step which determines the outcome in a visuospatial working memory (VSWM) task. It is considered to play a crucial role in limiting our ability to attend and process only 3-5 integrated items of information. Despite its importance in determining VSWM performance, the neural mechanisms underlying VSWM encoding have not been clearly differentiated from those involved during VSWM retention, manipulation and/or retrieval. The high temporal resolution of electroencephalography (EEG) and improved spatial resolution with dense array data acquisition makes it an ideal tool to study the dynamics in the functional brain connectivity during a cognitive task. In the present study, the changes in the functional brain connectivity due to memory load during VSWM encoding were studied using 128-channel EEG. Lagged linear coherence (LagR) was computed between 84 regions of interest (ROIs) defined according to the Brodmann areas for seven EEG frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-45 Hz). Interestingly, out of seven EEG frequency bands investigated in the current study, LagR of only theta band varied significantly in 13 brain connections due to memory load during VSWM encoding. LagR of theta band increased significantly at high memory load when compared to low memory load in twelve brain connections with the maximum change observed between right cuneus and right middle temporal gyrus (Cohen's d = 0.836), indicating the integration of brain processes to confront the increase in memory demands. Theta LagR decreased significantly between left postcentral gyrus and right precentral gyrus at high memory load as compared to low memory load, which might have a role for sustaining attention during encoding. Change in the LagR values due to memory load between fusiform gyrus and lingual gyrus in the right hemisphere had a positive correlation (r = 0.464, p = 0.003) with the error rate, signifying the crucial role played by these two regions in predicting the performance. The current study has not only identified the neural connections that are responsible for the formation of working memory traces during VSWM encoding, but also support the notion that encoding is a rate-limiting process underlying our memory capacity limit.

Cingulate oscillatory activity reflects the quality of memory representations in visuospatial working memory.

The human brain has the high likelihood for committing errors when confronted by a day-to-day situation that demands to process more than four integrated items in working memory, for example driving a car to a new destination in high traffic. However, neural mechanisms underlying the response outcome in working memory is still unclear. High temporal resolution and improved spatial resolution of dense array electroencephalogram (EEG) make it an ideal tool to investigate the dynamics of brain networks. In the present study, the brain activity of twenty healthy male volunteers was investigated during correct and error trials of visuospatial working memory task using dense array EEG. Independent brain components were identified using independent component analysis (ICA). Event-related spectral perturbations (ERSP) were computed for each independent component using Morlet wavelet transform for the frequency range of 3-70 Hz. ERSP of independent component clusters identified using K-means algorithm were statistically compared between correct and error trials. Delta and theta power increased in the component cluster located at cingulate gyrus before the error response of visuospatial working memory task. The current study findings suggest that cingulate oscillatory activity might reflect the quality of memory representation and intensity of target uncertainty during the visuospatial search.

Comparison of two formats of journal club for postgraduate students at two centers in developing critical appraisal skills.

Journal club (JC) is an integral part of postgraduate medical education. Although several innovations have been attempted to improve its effectiveness, the influence of the number of sessions remains unexplored. The current study investigated the effect of the number of sessions (one vs. four) of conduction of journal club on critical appraisal skills of postgraduate students at two institutions. A quasi-experimental study was conducted comparing the effectiveness of JC in a one- versus four-session JC format using two objective tests: Critical Appraisal Skills Test (CAST) and Population, Intervention, Comparison, Outcome (PICO) score. The degree of changes (pre-JC vs. post-JC session) after each format exposure, association of prescores to postscores, and correlation between the CAST and PICO scores were discerned. CAST score was higher in the four-session format (P = 0.03), whereas PICO score increased in the single-session format of JC (P = 0.03). Also, the change in CAST score was higher in the four-session versus single-session JC format (P = 0.04). We conclude that a four-session format of JC is more effective in augmenting critical appraisal skills of postgraduate students, whereas a single session is sufficient for improving factual knowledge.

Does valence influence perceptual bias towards incongruence during binocular rivalry?

The efficient processing of complex visual environments is essential for effective functioning. In the natural environment, processing the context is as important as the processing of the target object since no object can be found in isolation. Congruent object-context associations in a visual scene facilitate object recognition, whereas incongruent associations decrease performance accuracy. Although there is a performance reduction, incongruent scenes are reported to have a perceptual bias due to the reallocation of the attentional resources towards the associated semantic conflict. Another key attribute that prepares the visual system to identify the important aspects of the environment is valence, and any visual scene can be classified into one of the three valence categories. Hence, the current study was designed to investigate how valence influences the perceptual bias towards incongruent object-context associations. An intermittent binocular rivalry task was used to measure the perceptual bias across valence categories. The results revealed a significant predominance of incongruent pictures when the associated valence was negative and neutral and remained unbiased for positive valence. We propose a valence-congruency interaction in which perceptual bias towards incongruence is greatly influenced by valence.

Saccadic Eye Movements in Young-Onset Parkinson's Disease - A BOLD fMRI Study.

The objective of the present study was to understand control of saccadic eye movements in patients with young onset Parkinson's disease (YOPD) where onset of disease symptoms appears early in life (<40 years of age). Functional magnetic resonance imaging (fMRI) was performed in patients with YOPD and control subjects while they performed saccadic tasks, which consisted of a reflexive task and another task that required inhibitory control of eye movements (Go-NoGo task). Functional imaging related to saccadic eye movements in this group of patients has not been widely reported. A 1.5T MR scanner was used for structural and functional imaging. Analysis of blood-oxygen-level-dependent (BOLD) fMRI was performed using Statistical Parametric Mapping (SPM) software and compared in patients and controls. In patients with YOPD greater activation was seen significantly in the middle frontal gyrus, medial frontal gyrus, angular gyrus, cingulate gyrus, precuneus and cerebellum, when compared with the control group, during the saccadic tasks. Gap and overlap protocols revealed differential activation patterns. The abnormal activation during reflexive saccades was observed in the overlap condition, while during Go-NoGo saccades in the gap condition. The results suggest that impaired circuitry in patients with YOPD results in recruitment of more cortical areas. This increased frontal and parietal cortical activity possibly reflects compensatory mechanisms for impaired cognitive and saccadic circuitry.

Deactivation of default-mode network and early suppression of decision-making areas during retrieval period by high-arousing emotions improves performance in verbal working memory task.

Emotions affect many aspects of cognition (attention, decision-making, problem solving, conflict resolution, task switching, social cognition, etc.), but the cortical areas or networks through which these effects are achieved are still debatable. In the present study, the effect of emotion on cognition was studied in healthy young individuals (n = 56). Emotions were induced using high-arousing negative, positive, and low-arousing neutral pictures from the International Affective Picture System (IAPS). Sternberg's verbal working memory task was administered at baseline and after each emotion exposure, while high-density EEG was recorded. Cortical sources were calculated using sLORETA in the 500-ms window (for every 100 ms bin) before the response and were compared with baseline. Though the number of correct responses were comparable, reaction times after emotion exposure reduced significantly. Source analysis revealed significant deactivation of default mode network (DMN) areas as well as early deactivation of decision-making areas during Sternberg's task performed after both the negative and positive emotions. This early deactivation, much before the response was made, when compared with baseline suggests that tasks performed under high-arousing emotional states may help in making decisions earlier or faster. We conclude that the exposure to high-arousing emotional stimuli improves verbal working memory by helping in directing the attentional resources toward the task, thus decreasing the decision-making time and further suppressing the DMN areas.

Molecular genotyping of clinically important blood group antigens in patients with thalassaemia.

BACKGROUND & OBJECTIVES: In multitransfused thalassaemic patients, haemagglutination fails to phenotype the patient's blood group antigens due to the presence of donor-derived erythrocytes. DNA-based methods can overcome the limitations of haemagglutination and can be used to determine the correct antigen profile of these patients. This will facilitate the procurement of antigen-matched blood for transfusion to multitransfused patients. Thus, the aim of this study was to compare the serological phenotyping of common and clinically important antigens of Rh, Duffy, Kell, Kidd and MNS blood group systems with molecular genotyping amongst multitransfused thalassaemic patients. METHODS: Blood samples from 200 patients with thalassaemia and 100 'O' group regular blood donors were tested using standard serological techniques and polymerase chain reaction-based methods for common antigens/alleles (C, c, D, E, e, Fya, Fyb, Jka, Jkb, K, k, M, N, S, s). RESULTS: Genotyping and phenotyping results were discordant in 77 per cent of thalassaemic patients for five pairs of antithetical antigens of Rh, Duffy, Kell and Kidd blood group systems. In the MNS blood group system, 59.1 per cent of patients showed discrepancy. The rate of alloimmunization among thalassaemics was 7.5 per cent. INTERPRETATION & CONCLUSIONS: Molecular genotyping enabled the determination of the actual antigen profile in multitransfused thalassaemia patients. This would help reduce the problem of alloimmunization in such patients and would also aid in the better management of transfusion therapy.

Comparison of Tissue Elastography With Magnetic Resonance Imaging T2* and Serum Ferritin Quantification in Detecting Liver Iron Overload in Patients With Thalassemia Major.

BACKGROUND & AIMS: We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. METHODS: We conducted a prospective study of 154 patients (99 male; mean age, 12 ± 3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015. We performed routine blood sample analyses, measurements of serum levels of ferritin, and TE within 1 month of MRI T2* analysis of the liver. The Spearman correlation test and linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and R2* MRI results or serum ferritin levels. RESULTS: The subjects' mean total serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, and albumin were 1.4 ± 0.6 mg/dL, 65.0 ± 51.8 IU/L, 62.9 ± 44 IU/L, and 4.2 ± 0.2 g/d, respectively. Mean liver stiffness measurement, MRI T2* (3 T), corresponding MRI R2* (3 T), and ferritin values were 8.2 ± 4.4 kPa, 3.18 ± 2.6 milliseconds, 617.3 ± 549 Hz, and 4712 ± 3301 ng/mL, respectively. On the basis of MRI analysis, 67 patients (43.5%) had mild iron overload, 49 patients (31.8%) had moderate iron overload, and 22 patients (14.3%) had severe iron overload. Fibroscan liver stiffness measurements correlated with MRI R2* values (r = 0.85; P < .001). TE results identified the patients with severe, moderate, and mild iron overload with area under the receiver operating characteristic curve values of 94.8%, 84.5%, and 84.7%, respectively. Liver stiffness measurements greater than 13.5, 7.8, and 5.5 kPa identified patients with severe, moderate, and mild iron overload, respectively; the sensitivity and specificity values were 92% and 93% for severe overload, 82% and 82% for moderate overload, and 73% and 75% for mild overload. No correlation was found between TE results and serum level of ferritin (r = 0.19; P = .11). CONCLUSIONS: Results of TE correlate with those from MRI T2* analysis. TE is cheaper and more available than MRI and might be used to estimate hepatic iron overload, especially moderate to severe overload in patients with thalassemia major who require chronic transfusion.

Individual Alpha Frequency (IAF) Based Quantitative EEG Correlates of Psychological Stress.

OBJECTIVES: To explore the EEG changes associated with psychological stress state. METHODS: The study was conducted on 34 healthy male student volunteers. The intervention consisted of psychological stress, which was induced by asking the participants to play a pre-decided stressful computer game. Physiological markers of psychological stress were assessed using galvanic skin response (GSR) and heart rate (HR). Electroencephalography (EEG) was recorded from 19 scalp locations according to 10-20 international system of electrode placement. RESULTS: Computer game served as model of lab stressor and was associated with a significant increase in physiological markers (GSR & heart rate) of stress response. Psychological stress was associated with increased absolute power in theta, lower 1 alpha and gamma bands & decreased power in upper alpha and beta bands. Lower 2 alpha band power remained unchanged. CONCLUSIONS: Certain types of computer games serve as a model of lab stressor and are associated with physiological and psychological stress and have unique electroencephalographic correlates. The EEG correlates of mental stress are unique superimposed pattern of various cognitive domains. With sustained and continuing stress resulting from computer game attention, alertness and performance starts declining.

Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study.

INTRODUCTION: Ocimum sanctum (OS), known as Holy basil, has been documented to possess neuroprotective, cognition-enhancing and stress relieving effects in animal models. However there is paucity of clinical studies to document these effects. MATERIALS AND METHODS: Effect of OS on parameters related to cognition and stress in humans was evaluated with administration of 300 milligram capsules of ethanolic leaf extracts of Ocimum sanctum (EtOS) or placebo per day, over 30 days. RESULTS: Intra-group comparison of Sternberg and Stroop test showed improvement in both the placebo and EtOS groups, however, the improvement stabilized after day 15 in the placebo group. Intergroup comparison revealed a significant improvement of the following cognitive parameters in the EtOS as compared to the placebo: reaction time (RT) and error rate (ER) of Sternberg test, RT of neutral task of Stroop, RT and ER of interference task of Stroop. The intra-group comparison of P300 latency, salivary cortisol, and State-Trait Anxiety Inventory showed improvement over time in the EtOS group alone, though the inter-group difference was significant in the P300 latency alone. There were no changes in heart rate (HR), AHR, or galvanic skin response (GSR) or AGSR. CONCLUSION: Ocimum sanctum leaf extract seems to have potential cognition-enhancing properties in humans.

Physiological Consequences of Nonsense-Mediated Decay and Its Role in Adaptive Responses.

The evolutionarily conserved nonsense-mediated mRNA decay (NMD) pathway is a quality control mechanism that degrades aberrant mRNA containing one or more premature termination codons (PTCs). Recent discoveries indicate that NMD also differentially regulates mRNA from wild-type protein-coding genes despite lacking PTCs. Together with studies showing that NMD is involved in development and adaptive responses that influence health and longevity, these findings point to an expanded role of NMD that adds a new layer of complexity in the post-transcriptional regulation of gene expression. However, the extent of its control, whether different types of NMD play different roles, and the resulting physiological outcomes remain unclear and need further elucidation. Here, we review different branches of NMD and what is known of the physiological outcomes associated with this type of regulation. We identify significant gaps in the understanding of this process and the utility of genetic tools in accelerating progress in this area.

In vitro activity of cefiderocol against comparators (ceftazidime-avibactam, ceftazidime-avibactam/ aztreonam combination, and colistin) against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India.

Cefiderocol (FDC), a novel siderophore drug, is active against Gram-negative bacteria producing carbapenemases, including metallo-beta-lactamases. The objective of this study is to compare the in vitro activity of FDC with ceftazidime-avibactam (CZA), CZA/aztreonam (AT) combination, and colistin (CST), in clinical isolates of meropenem-resistant (MER-R) Klebsiella pneumoniae. From the 2,052 clinical specimens submitted for culture testing, 245 K. pneumoniae isolates were recovered within a 6-month period in 2021. One hundred three non-duplicate, non-outbreak, MER-R (minimum inhibitory concentration, MIC >4 µg/mL) strains were included in the study. Identification and susceptibility were performed using VITEK-2 (bioMérieux). Meropenem-susceptible isolates (n = 10) served as controls. For FDC, broth microdilution (BMD) was performed after in-house standardization. Disk diffusion (Liofilchem, Italy) and broth microdilution (ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST, respectively. Synergy testing for CZA and AT was performed using disk approximation method. CLSI breakpoints were used for the interpretation of the results. For FDC, MIC50 and MIC90 were 2 and 8 µg/mL, respectively. A total of 80% of isolates were susceptible to FDC, 26.2% of isolates were susceptible to CZA, synergy testing with CZA/AT was positive for 74 (72%) of the isolates, and 89.3% were intermediate to CST. Nine (8.7%) were susceptible only to FDC. FDC is active in vitro against MER-R K. pneumoniae >CZA/AT > CZA > CST, as observed in this study, applying CLSI criteria. Clinico-microbiological studies should be performed to assess the clinical efficacy of this novel drug in this region with a high prevalence of carbapenem resistance among Gram-negative organisms. IMPORTANCE Management of infections with multi-drug resistant Klebsiella pneumoniae is a major challenge in hospital settings, with few treatment options. In this study, the authors aim to assess the in vitro susceptibility of these clinical isolates to cefiderocol, a novel siderophore. Comparators are colistin, ceftazidime-avibactam, and ceftazidime-avibactam/aztreonam synergy, which are currently available options for treatment in this region. Baseline-resistance rates against cefiderocol are higher than those in the previously published studies, with MIC50 and MIC90 at 2 and 8 µg/mL, respectively.

Immediate and long-term effects of meditation on acute stress reactivity, cognitive functions, and intelligence.

CONTEXT: With the current globalization of the world's economy and demands for enhanced performance, stress is present universally. Life's stressful events and daily stresses cause both deleterious and cumulative effects on the human body. The practice of meditation might offer a way to relieve that stress. OBJECTIVE: The research team intended to study the effects of meditation on stress-induced changes in physiological parameters, cognitive functions, intelligence, and emotional quotients. METHODS: The research team conducted the study in two phases, with a month between them. Each participant served as his own control, and the first phase served as the control for the second phase. In phase 1, the research team studied the effects of a stressor (10 minutes playing a computer game) on participants' stress levels. In phase 2, the research team examined the effects of meditation on stress levels. SETTING: The research team conducted the study in a lab setting at the All India Institute of Medical Sciences (AIIMS), New Delhi, India. PARTICIPANTS: The participants were 34 healthy, male volunteers who were students. INTERVENTION: To study the effects of long-term meditation on stress levels, intelligence, emotional quotients, and cognitive functions participants meditated daily for 1 month, between phases 1 and 2. To study the immediate effects of meditation on stress levels, participants meditated for 15 minutes after playing a computer game to induce stress. OUTCOME MEASURES: The research team measured galvanic skin response (GSR), heart rate (HR), and salivary cortisol and administered tests for the intelligence and emotional quotients (IQ and EQ), acute and perceived stress (AS and PS), and cognitive functions (ie, the Sternberg memory test [short-term memory] and the Stroop test [cognitive flexibility]). Using a pre-post study design, the team performed this testing (1) prior to the start of the study (baseline); (2) in phase 1, after induced stress; (3) in part 1 of phase 2, after 1 month of daily meditation, and (4) in part 2 of phase 2, after induced stress, both before and after 15 minutes of meditation. RESULTS: Induced stress from the computer game resulted in a significant increase in physiological markers of stress such as GSR and HR. In the short term, meditation was associated with a physiological relaxation response (significant decrease in GSR) and an improvement in scores on the Stroop test of reaction times. In the long-term, meditation brought significant improvements in IQ and scores for cognitive functions, whereas participants' stress levels (GSR and AS) decreased. EQ, salivary cortisol, and HR showed no significant changes. CONCLUSIONS: The practice of meditation reduced psychological stress responses and improved cognitive functions, and the effects were pronounced with practice of meditation for a longer duration (1 month).

Placebo-Related Adverse Events in Rheumatoid Arthritis.

Prospective, double-blind, randomized, placebo-controlled studies are considered to provide the highest quality of interventional evidence. This meta-analysis summarizes the frequencies of adverse events according to the Medical Dictionary for Regulatory Activities (MedDRA) in the placebo arms of 101 such studies in rheumatoid arthritis, including a total of 17,150 patients in the placebo arms and 37,819 patients in the verum arms. Placebo-treated patients reported more than one adverse event in a median of 55.0%, 65.5%, and 72.5% (compared to 72.3% in the verum arms), and a serious adverse event in 2.5%, 5.8%, and 8.6% (compared to 5.9% in the verum arms), with stable doses of corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs as background therapies, respectively. Odds ratios were comparable between placebo and verum arms for nausea (1.00 with 95% confidence interval (CI) 0.86-1.17), for hepatobiliary disorders (1.08 with CI 0.85-1.36), for abnormal hepatic functions (1.09 with CI 0.83-1.44), and general disorders and administration site conditions (1.39 with CI 0.95-2.03). A publication bias has to be assumed for nausea (p = 0.018; Egger's test), diarrhoea (p = 0.022), and serious infections and infestations (p = 0.009). In conclusion, patients should be aware that "adverse events" may occur even with placebo medication, independent from an additional verum medication added to the background therapy. Further studies are warranted to respect and overcome the psychological and other issues related to these placebo-related "adverse events".