A Two-Step Approach to Overcoming Data Imbalance in the Development of an Electrocardiography Data Quality Assessment Algorithm: A Real-World Data Challenge.

Continuously acquired biosignals from patient monitors contain significant amounts of unusable data. During the development of a decision support system based on continuously acquired biosignals, we developed machine and deep learning algorithms to automatically classify the quality of ECG data. A total of 31,127 twenty-s ECG segments of 250 Hz were used as the training/validation dataset. Data quality was categorized into three classes: acceptable, unacceptable, and uncertain. In the training/validation dataset, 29,606 segments (95%) were in the acceptable class. Two one-step, three-class approaches and two two-step binary sequential approaches were developed using random forest (RF) and two-dimensional convolutional neural network (2D CNN) classifiers. Four approaches were tested on 9779 test samples from another hospital. On the test dataset, the two-step 2D CNN approach showed the best overall accuracy (0.85), and the one-step, three-class 2D CNN approach showed the worst overall accuracy (0.54). The most important parameter, precision in the acceptable class, was greater than 0.9 for all approaches, but recall in the acceptable class was better for the two-step approaches: one-step (0.77) vs. two-step RF (0.89) and one-step (0.51) vs. two-step 2D CNN (0.94) (p < 0.001 for both comparisons). For the ECG quality classification, where substantial data imbalance exists, the 2-step approaches showed more robust performance than the one-step approach. This algorithm can be used as a preprocessing step in artificial intelligence research using continuously acquired biosignals.

In Vitro Activity of Two Cefepime-Based Novel Combinations, Cefepime/Taniborbactam and Cefepime/Zidebactam, against Carbapenemase-Expressing Enterobacterales Collected in India.

In recent times, discovery efforts for novel antibiotics have mostly targeted carbapenemase-producing Gram-negative organisms. Two different combination approaches are pertinent: ß-lactam-ß-lactamase inhibitor (BL/BLI) or ß-lactam-ß-lactam enhancer (BL/BLE). Cefepime combined with a BLI, taniborbactam, or with a BLE, zidebactam, has been shown to be promising. In this study, we determined the in vitro activity of both these agents along with comparators against multicentric carbapenemase-producing Enterobacterales (CPE). Nonduplicate CPE isolates of Escherichia coli (n = 270) and Klebsiella pneumoniae (n = 300), collected from nine different tertiary-care hospitals across India during 2019 to 2021, were included in the study. Carbapenemases in these isolates were detected by PCR. E. coli isolates were also screened for the presence of the 4-amino-acid insert in penicillin binding protein 3 (PBP3). MICs were determined by reference broth microdilution. Higher MICs of cefepime/taniborbactam (>8 mg/L) were linked to NDM, both in K. pneumoniae and in E. coli. In particular, such higher MICs were observed in 88 to 90% of E. coli isolates producing NDM and OXA-48-like or NDM alone. On the other hand, OXA-48-like-producing E. coli or K. pneumoniae isolates were nearly 100% susceptible to cefepime/taniborbactam. Regardless of the carbapenemase types and the pathogens, cefepime/zidebactam showed potent activity (>99% inhibited at ≤8 mg/L). It seems that the 4-amino-acid insert in PBP3 (present universally in the study E. coli isolates) along with NDM adversely impact the activity of cefepime/taniborbactam. Thus, the limitations of the BL/BLI approach in tackling the complex interplay of enzymatic and nonenzymatic resistance mechanisms were better revealed in whole-cell studies where the activity observed was a net effect of ß-lactamase inhibition, cellular uptake, and target affinity of the combination. IMPORTANCE The study revealed the differential ability of cefepime/taniborbactam and cefepime/zidebactam in tackling carbapenemase-producing Indian clinical isolates that also harbored additional mechanisms of resistance. NDM-expressing E. coli with 4-amino-acid insert in PBP3 are predominately resistant to cefepime/taniborbactam, while the ß-lactam enhancer mechanism-based cefepime/zidebactam showed consistent activity against single- or dual-carbapenemase-producing isolates including E. coli with PBP3 inserts.

A Case of Idiopathic Retinitis Vasculitis Aneurysms and Neuroretinitis (IRVAN) Treated with Adalimumab.

PURPOSE: To report a case of IRVAN in a 13-year-old girl responding well to Adalimumab and Azathioprine. RESULTS: A 13-year-old girl presented to us with central scotoma for a duration of 10 months. She was treated earlier with oral steroids with poor response. Fundus examination revealed features of IRVAN. She was treated with intravitreal dexamethasone implant in both eyes with oral Mycophenolate Mofetil (MMF) with transient response to it. So she was switched over to subcutaneous Adalimumab 40 mg once in 2 weeks and oral Azathioprine 50 mg BD. The disease activity was well controlled with the current regime. CONCLUSION: Though various treatment modalities have been described in literature for the treatment of IRVAN. This is the first case of IRVAN to be treated with Adalimumab along with Azathioprine to be reported.

Synaptic correlates of associative fear memory in the lateral amygdala.

Successful adaptation to the environment requires an accurate response to external threats by recalling specific memories. Memory formation and recall require engram cell activity and synaptic strengthening among activated neuronal ensembles. However, elucidation of the underlying neural substrates of associative fear memory has remained limited without a direct interrogation of extinction-induced changes of specific synapses that encode a specific auditory fear memory. Using dual-eGRASP (enhanced green fluorescent protein reconstitution across synaptic partners), we found that synapses among activated neuronal ensembles or activated synaptic ensembles showed a significantly larger spine morphology at auditory cortex (AC)-to-lateral amygdala (LA) projections after auditory fear conditioning in mice. Fear extinction reversed these enhanced synaptic ensemble spines, whereas re-conditioning with the same tone and shock restored the spine size of the synaptic ensemble. We suggest that synaptic ensembles encode and represent different fear memory states.

Alternate PCR assays for screening of JH1 mutation associated with embryonic death in Jersey cattle.

Jersey haplotype (JH) 1, a stop-gain lethal mutation in the CWC15 gene, causes embryonic losses in Jersey cattle. Two PCR based assays using Amplification Refractory Mutation System (T-ARMS-PCR) and restriction fragment length polymorphism (PCR-RFLP) were developed for screening of the JH1 in cattle. During the screening, seven among 30 Indian Jersey bulls were identified as carriers of the mutant JH1 allele, the first time in the country. These PCR assays are economical, rapid and accurate; and can be used separately or in combination for screening and cross-validation of the JH1 carriers in Jersey cattle.

Retroperitoneal approach for dissection of inflamed pelvic viscera in acute pelvic inflammatory disease- case report.

Tubo-ovarian abscesses can rupture spontaneously after a manual examination or an accidental trauma. A critically ill patient with septic peritonitis will only deteriorate if timely surgical removal of pus is not done. The operation of choice is removal of free pus, together with the abscess, the uterus, the tubes and usually, the ovaries. Anatomy is distorted, dependable landmarks are obscured and tissues are thick and oedematous. Loops of densely adhered intestine are difficult to separate. If an intra peritoneal approach is used, it is likely that the fragments of ovary will be left behind. This can subsequently cause signs and symptoms of ovarian remnant syndrome. Injury to the serosa of distended bowel occurs inadvertently, thus increasing the morbidity which results from the procedure. We are hereby presenting a unique case of a ruptured tubo-ovarian abscess where a retroperitoneal approach was used.

Prevalence of High and Low Level Mupirocin Resistance among Staphylococcal Isolates from Skin Infection in a Tertiary Care Hospital.

BACKGROUND: Mupirocin has been used for the treatment of skin infections and for the eradication of the nasal carriage of Methicillin -resistant Staphylococcus aureus (MRSA). The increased use of this antibiotic has been accompanied by its resistance, resulting in treatment failures. OBJECTIVE: This study was aimed at determining the prevalences of low and high level Mupirocin resistance among the clinical isolates of Staphylococcus species which were obtained from pyogenic infections. MATERIAL AND METHOD: Clinical samples such as wound swabs, tissues and pus which were submitted to the microbiology laboratory during a period of six months were screened for the growth of Staphylococcus species, which were identified as Staphylococcus aureus and Coagulase negative Staphylococcus species by the routine microbiological procedures. All the isolates were tested for their Mupirocin susceptibilities by using 5 and 200 µg discs and their resistance was confirmed from their Minimum Inhibitory Concentrations (MICs). RESULT: Out of 400 samples, 150 samples grew Staphylococcus species, of which 113 were Staphylococcus aureus and 37 were Coagulase negative Staphylococcus (CoNS). Only 5(3.3%) mupirocin resistant Staphylococcus species: three high level and two low level strains were detected. The MICs for the two low level and three high level Mupirocin resistant strains were 256 mg/L and ≥512mg/L each respectively. CONCLUSION: We conclude that the screening for mupirocin resistance, in terms of high-level and low-level resistance among the Staphylococcus species from patients with skin and soft tissue infections is warranted and that it is important for the clinicians in selecting the appropriate, empirical, topical, antimicrobial therapy. It also provides useful information about the prevalence of these resistant pathogens.