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Background: The current coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge that has caused morbidity and mortality at unprecedented levels. Studies have estimated that approximately 10% of all patients who have recovered from COVID-19 are suffering from persistent symptoms of cough, dyspnea, and fatigue over months after the acute infection. Many patients reported persistent airway symptoms post-COVID. Since the post-COVID pulmonary complications are evolving and challenging, a study was carried out to assess post-COVID new-onset asthma in adults. Objectives: To assess the incidence of new-onset asthma following COVID-19 in adults. Methods: A prospective observational study including all adult patients admitted or treated on an out patient department (OPD) basis for COVID-19 was carried out. All patients on follow-up who reported with airway symptoms (cough, wheezing, breathlessness, or chest tightness) with no prior diagnosed obstructive/restrictive airway disease were included in the study and followed up for a duration of 01 years. New-onset asthma was diagnosed based on symptomatology and assessed as per Global Initiative for Asthma guidelines. Results: Among 411 patients with airway symptoms post-COVID-19, 9.4% (n = 97) developed new-onset bronchial asthma on follow-up. Conclusion: Asthma in patients’ post-COVID-19 disease is not uncommon, and detailed evaluation and follow-up are instrumental in instituting timely and correct therapy and in providing symptomatic relief to patients.

BACKGROUND: Tuberculosis is an important public healthcare problem in our country. Drug-resistant Tuberculosis is like a smoldering fire that if not controlled will flare up to an uncontrolled inferno. The conventional therapy for multidrug-resistant TB is associated with multiple issues like prolonged duration and various side effects. Newer anti-tubercular drugs are available but there is a lack of real-world evidence of their use. Bedaquiline is a novel drug belonging to the dairlyquinolone group. It has a bactericidal action and works by inhibiting the mycobacterial ATP synthase enzyme limiting the provision of ATP to mycobacterium. METHODS: This was an observational study done at a tertiary respiratory care center on MDR TB patients to study the efficacy and adverse event profile of Bedaquiline in a clinical setting by examining the culture and smear conversion time. RESULTS: 30 patients with MDR TB were included in the study. 28 patients had Kat G mutation of Isoniazid while 2 patients had InH A resistance. The second line probe assay showed additional resistance to fluoroquinolones in 27 patients and 2 patients had resistance to aminoglycosides. Twenty-one patients were on the first line while 9 patients were on second-line ATT drugs at the time of presentation to our center. The median smear conversion time was 4 weeks while the median culture conversion time was 10 weeks. The average weight gain was 9 kilograms. All patients recovered with a 100 % success rate. There were no life-threatening adverse effects noted, while two patients developed prolonged QTc on ECG. However, the QTc interval was less than 500 ms, and thus bedaquiline was not discontinued. CONCLUSION: Our study aims to highlight the use of Bedaquiline-based anti-tubercular therapy in drug-resistant tuberculosis.

Pulmonary sequestration is an uncommon congenital anomaly. It is usually diagnosed at a young age but can present in adults with recurrent episodes of pneumonia and cough. Isolated shortness of breath is an uncommon presentation of pulmonary sequestration and is rarely reported. We describe an adult male who presented with exertional dyspnea at a high altitude and was eventually diagnosed as a case of pulmonary sequestration. It is an uncommon developmental anomaly that can go undetected at a young age. In adults, it can present as isolated dyspnea, and a thorough work-up can lead to an accurate diagnosis.

Background: B-cell receptor (BCR) signaling is a central driver in chronic lymphocytic leukemia (CLL), along with the activation of pro-survival pathways (e.g., NF-κB) and aberrant anti-apoptotic mechanisms (e.g., BCL2) culminating to CLL cell survival and drug resistance. Front-line targeted therapies such as ibrutinib (BTK inhibitor) and venetoclax (BCL2 inhibitor) have radically improved CLL management. Yet, persisting CLL cells lead to relapse in ~20% of patients, signifying the unmet need of inhibitor-resistant refractory CLL. SpiD3 is a novel spirocyclic dimer of analog 19 that displays NF-κB inhibitory activity and preclinical anti-cancer properties. Recently, we have shown that SpiD3 inhibits CLL cell proliferation and induces cytotoxicity by promoting futile activation of the unfolded protein response (UPR) pathway and generation of reactive oxygen species (ROS), resulting in the inhibition of protein synthesis in CLL cells. Methods: We performed RNA-sequencing using CLL cells rendered resistant to ibrutinib and venetoclax to explore potential vulnerabilities in inhibitor-resistant and SpiD3-treated CLL cells. Results: The transcriptomic analysis of ibrutinib- or venetoclax-resistant CLL cell lines revealed ferroptosis, UPR signaling, and oxidative stress to be among the top pathways modulated by SpiD3 treatment. By examining SpiD3-induced protein aggregation, ROS production, and ferroptosis in inhibitor-resistant CLL cells, our findings demonstrate cytotoxicity following SpiD3 treatment in cell lines resistant to current front-line CLL therapeutics. Conclusions: Our results substantiate the development of SpiD3 as a novel therapeutic agent for relapsed/refractory CLL disease.

This paper presents a compact and planar, in-band full-duplex antenna that offers significant isolation across a broad range of frequencies. In order to attain a wide impedance bandwidth within a limited physical space, two half-resonating modes of a microstrip patch antenna (MPA), namely TM $_{\mathrm {0,3/2}}$ and TM $_{\mathrm {1,1/2}}$ , are stimulated in close proximity. Moreover, the utilization of a parasitic strip that acts as a $\lambda $ /2 resonator, assists in increasing the inter-port isolation. A prototype is fabricated and further measurements indicate that the proposed design offers inter-port isolation better than 30 dB across its wide operating band of 5.95-6.47 GHz, which corresponds to approximately 9% impedance bandwidth ( $\vert $ S $_{11}\vert $ , $\vert $ S $_{22}\vert \lt -10$ dB). Additionally, the prototype exhibited a significant peak gain of 8.2 dBi.

Background: Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic success in CLL has been stifled by its pro-tumor microenvironment milieu and low mutational burden, cultivating poor antigenicity and limited ability to generate anti-tumor immunity through adaptive immune cell engagement. Previously, we have demonstrated how a three-carbon-linker spirocyclic dimer (SpiD3) promotes futile activation of the unfolded protein response (UPR) in CLL cells through immense misfolded-protein mimicry, culminating in insurmountable ER stress and programmed CLL cell death. Method: Herein, we used flow cytometry and cell-based assays to capture the kinetics and magnitude of SpiD3-induced damage-associated molecular patterns (DAMPs) in CLL cell lines and primary samples. Result: SpiD3 treatment, in vitro and in vivo, demonstrated the capacity to propagate immunogenic cell death through emissions of classically immunogenic DAMPs (CALR, ATP, HMGB1) and establish a chemotactic gradient for bone marrow-derived dendritic cells. Conclusions: Thus, this study supports future investigation into the relationship between novel therapeutics, manners of cancer cell death, and their contributions to adaptive immune cell engagement as a means for improving anti-cancer therapy in CLL.

Ewing’s sarcoma (ES) is a rare and highly aggressive tumour of neuroectodermal origin. Primary pulmonary ES is extremely rare and difficult to distinguish from other lung tumours due to its similar presentation and nonspecific symptoms. It requires a deliberate interplay of imaging, histopathological exam, immunohistochemistry (IHC) and genetic analysis to confirm the diagnosis. Here we present a rare case of extra osseus ES.

We report a case of a 32-year-old male with a history of type 1 diabetes, inhaled drug use, and alcohol use disorder, who presented with encephalopathy, holocranial headaches, neck pain, confusion, and generalized tonic-clonic seizures. The patient initially presented at a rural community hospital with a fever and was found to be in diabetic ketoacidosis (DKA). He was also hemodynamically stable but stuporous, prompting intubation to protect his airway. Despite initial treatment measures, his neurological condition worsened and he remained ventilator-dependent. Key findings include a high glucose level, presence of ketones, and evidence of drug use. Blood cultures showed no growth, but his febrile state persisted. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis, hyperglycorrhachia but normal protein, with no growth. Neuroimaging showed right hemispheric slowing on EEG and diffusion restriction in the right frontal lobe on MRI. The patient's neurological status worsened on the second day of admission, manifesting as sluggish pupillary reflexes, right third nerve palsy, and decerebrate posturing. Emergent MRI suggested cerebral edema, leading to initiation of hypertonic saline. This case highlights the diagnostic challenges and critical management considerations in a patient with multiple comorbidities presenting with unexplained neurological deterioration, emphasizing the importance of a comprehensive and timely approach to diagnosis and treatment.

Regulation of post translational modification of 53BP1 is critical for genome integrity and regulation of DNA damage response. Here the authors reveal a CDK5-PP4 phospho-signaling cascade that leads 53BP1 to sites of DNA damage.

Synthetic lethality is a successful strategy employed to develop selective chemotherapeutics against cancer cells. Inactivation of RAD52 is synthetically lethal to homologous recombination (HR) deficient cancer cell lines. Replication protein A (RPA) recruits RAD52 to repair sites, and the formation of this protein-protein complex is critical for RAD52 activity. To discover small molecules that inhibit the RPA:RAD52 protein-protein interaction (PPI), we screened chemical libraries with our newly developed Fluorescence-based protein-protein Interaction Assay (FluorIA). Eleven compounds were identified, including FDA-approved drugs (quinacrine, mitoxantrone, and doxorubicin). The FluorIA was used to rank the compounds by their ability to inhibit the RPA:RAD52 PPI and showed mitoxantrone and doxorubicin to be the most effective. Initial studies using the three FDA-approved drugs showed selective killing of BRCA1-mutated breast cancer cells (HCC1937), BRCA2-mutated ovarian cancer cells (PE01), and BRCA1-mutated ovarian cancer cells (UWB1.289). It was noteworthy that selective killing was seen in cells known to be resistant to PARP inhibitors (HCC1937 and UWB1 SYr13). A cell-based double-strand break (DSB) repair assay indicated that mitoxantrone significantly suppressed RAD52-dependent single-strand annealing (SSA) and mitoxantrone treatment disrupted the RPA:RAD52 PPI in cells. Furthermore, mitoxantrone reduced radiation-induced foci-formation of RAD52 with no significant activity against RAD51 foci formation. The results indicate that the RPA:RAD52 PPI could be a therapeutic target for HR-deficient cancers. These data also suggest that RAD52 is one of the targets of mitoxantrone and related compounds.

Creutzfeldt–Jakob disease (CJD) is a well-described disease. It is characterized by rapidly progressive dementia, myoclonus, ataxia, pyramidal, and extrapyramidal signs. There are well-defined electroencephalogram and magnetic resonance imaging (MRI) findings, and markers found in the cerebrospinal fluid (CSF). The gold standard for diagnosing CJD remains brain biopsy. We present a case of a patient with a family history of biopsy-proven CJD who initially presented with symptoms of peripheral neuropathy. A month later, he developed ataxia, ophthalmoparesis, and then dysarthria. His initial workup was relatively unrevealing, showing an elevated protein in his CSF. He was thought to have Miller Fisher syndrome variant of Guillain–Barré syndrome. He neither, however, responded to plasmapheresis nor IVIG. He later started to develop progressive dementia. Repeated MRI showed restricted diffusion in the caudate and putamen, as well as in the cortex (cortical ribboning). Lumbar puncture was then found to be positive for 14-3-3 protein, total-tau protein, and real-time quaking-induced conversion assay, which are highly suggestive of CJD. We present a case of CJD with an unusual presentation resulting in misdiagnosis, prolonged workup, and potentially harmful treatment modalities. This case highlights the importance of broadening our definition of CJD to encompass more cases with unusual presentations.

Background: Fiberoptic bronchoscopy is very important tool for evaluating the profile of endobronchial lesion. Endobronchial profile provides important clue regarding likely pathology which is of immense help for clinician and pathologist to reach definitive diagnosis. Aim and Objectives: To study the clinical, radiological, and histopathological profile of endobronchial lesions detected during bronchoscopy. Materials and Methods: A cross-sectional prospective observational study was conducted at a tertiary respiratory center. Demographic, clinical, and radiological profile was prepared for all patients above 18 years of age, and relevant blood and radiological investigations were conducted. Patients detected to have endobronchial lesion during fiberoptic bronchoscopy were selected for the study. Bronchoalveolar lavage, bronchial biopsy, and bronchial brushing were done and sent for examination. Patients were observed postprocedure for any complication. Results: Male patients were more in number (70%) with most of patients above 40 years of age (80%). Most common symptom was cough (48%) with smoking history present in 48% patients. Mass lesion was most common radiological presentation (52%). Right lung was most commonly involved (52%), and upper lobe involvement was most common (50%). Exophytic growth was most common endobronchial lesion (46%) with carcinoma lung most common diagnosis (74%). Hemoptysis was most common complication (80%), which resolved on its own, followed by postprocedure hypoxemia (8%). Conclusion: Clinical, radiological, and bronchoscopic profile of endobronchial lesion is an important information which helps clinician and pathologist to reach final diagnosis. Carcinoma lung is most common diagnosis made in our study as most common endobronchial lesions at age of our patients are malignant as reported in literature.

Allergic bronchopulmonary mycosis (ABPM) is most commonly seen in cystic fibrosis and bronchial asthma. Most of patients are misdiagnosed at initial outpatient department visit due to low suspicion, lack of awareness of entity and similarity in clinical symptoms and radiological findings with other common pulmonary diseases. Pulmonary tuberculosis is the most common entity diagnosed, and anti-tubercular treatment is the most commonly abused chemotherapy. Careful history taking, astute initial examination and awareness may help in curbing wrong diagnosis and treatment. This article present two cases of ABPM who were initially misdiagnosed as pulmonary tuberculosis and carcinoma lung, respectively.

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents’ professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or resident characteristics were related to stress during the pandemic. Our secondary goals were to examine which resident characteristics were related to survey responses. Data were analyzed with regression analyses. Ninety-six of 205 residents completed the survey (47% response rate). For our primary outcome, anxiety about PPE (P 0.001). Additionally, compared to juniors, seniors believed that the pandemic was more disruptive, modified schedules were effective, and virtual meetings were less effective while virtual lectures were more effective (all P ≤ 0.05) Furthermore, the pandemic experience has allowed seniors in particular to feel more confident to lead in future health crises (P ≤ 0.05). Medicine and surgery residency programs should be cognizant of and closely monitor the effects of COVID-19 crisis-related factors on residents’ stress and anxiety levels. Transparent communication, telemedicine, online lectures/meetings, procedure simulations, advocacy groups, and wellness resources may help to mitigate some of the challenges posed by the pandemic.

Pulmonary embolism remains a disease which needs high clinical suspicion to prevent mortality and morbidity. More so in young healthy individuals, suspicion is very low as compared to old age individuals with multiple co-morbid conditions. Pulmonary embolism carries high mortality if not suspected and treatment initiated as early as possible. There are two case reports of young male individuals who presented as acute onset of breathlessness and later diagnosed and treated as a case of pulmonary thromboembolism.

Background and Aims: Face mask ventilation of the edentulous patient is often difficult as ineffective seating of the standard mask to the face prevents attainment of an adequate air seal. The efficacy of nasal ventilation in edentulous patients has been cited in case reports but has never been investigated. Material and Methods: Consecutive edentulous adult patients scheduled for surgery under general anesthesia with endotracheal intubation, during a 17-month period, were prospectively evaluated. After induction of anesthesia and administration of neuromuscular blocker, lungs were ventilated with a standard anatomical face mask of appropriate size, using a volume controlled anesthesia ventilator with tidal volume set at 10 ml/kg. In case of inadequate ventilation, the mask position was adjusted to achieve best-fit. Inspired and expired tidal volumes were measured. Thereafter, the face mask was replaced by a nasal mask and after achieving best-fit, the inspired and expired tidal volumes were recorded. The difference in expired tidal volumes and airway pressures at best-fit with the use of the two masks and number of patients with inadequate ventilation with use of the masks were statistically analyzed. Results: A total of 79 edentulous patients were recruited for the study. The difference in expiratory tidal volumes with the use of the two masks at best-fit was statistically significant (P = 0.0017). Despite the best-fit mask placement, adequacy of ventilation could not be achieved in 24.1% patients during face mask ventilation, and 12.7% patients during nasal mask ventilation and the difference was statistically significant. Conclusion: Nasal mask ventilation is more efficient than standard face mask ventilation in edentulous patients.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cerebral radiation therapy. A 53-year-old female initially presented with headache, confusion and left homonymous hemianopia. Her medical history was notable for cerebellar hemangioblastoma, which was treated with radiation in 1987. Her initial brain MRI (magnetic resonance imaging) revealed cortical enhancement in the right temporo-parieto-occipital region. She improved spontaneously in 2 weeks and follow-up scan at 4 weeks revealed no residual enhancement or encephalomalacia. She presented 6 weeks later with aphasia. Her MRI brain revealed similar contrast-enhancing cortical lesion but on the left side. Repeat CSF studies was again negative other than elevated protein. She was treated conservatively and recovered completely within a week. Before diagnosing SMART syndrome, it is important to rule out tumor recurrence, encephalitis, posterior reversible encephalopathy syndrome (PRES) and stroke. Typically the condition is self-limiting, and gradually resolves.

New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 microM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast ( approximately 30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species.

West Nile Virus (WNV) is an arthropod-borne flavivirus, which causes flu-like illness and is sporadically associated with encephalitis. Transmission to humans occurs following a bite from an infected mosquito, which acquires the virus after feeding on dead birds. WNV meningoencephalitis is a rare infection with a neuroinvasive disease occurring in less than 1% of the cases, with varied presentations including aseptic meningitis, meningoencephalitis, and acute flaccid paralysis. Chorioretinitis is the most common eye finding in this infection, while other ocular manifestations have been rarely reported in the literature. We present the first case report of WNV meningoencephalitis, with rare ocular manifestations of acute hemorrhagic conjunctivitis, bilateral subconjunctival hemorrhages, and nystagmus. The rare ocular findings of acute hemorrhagic conjunctivitis, bilateral subconjunctival hemorrhages, and nystagmus diagnosed in our case can guide clinicians toward early diagnosis of WNV meningoencephalitis, while serologic testing is still pending.

Exogenous lipoid pneumonia including diesel aspiration pneumonia is a challenging scenario for the physician view varied clinical presentation and no existing treatment guidelines. Clinico-radiological profiling remains the key toward early diagnosis of the condition. We present a case of a 32-year-old car mechanic presenting post accidental aspiration of diesel vehicle while siphoning air from the fuel pipe, a common practice in Indian subcontinent; highlighting the clinical and radiological presentation and therapeutic outcomes of corticosteroids in this case. The case reemphasizes the role of good clinical history, efficient physical examination, early management, and specific radiological evaluation toward management of this entity.

Abstract  Intrapericardial teratomas are rare after infancy. An accurate diagnosis can only be made with a high index of suspicion. Most of the time, a mediastinal teratoma ruptures/perforates the pericardial cavity, thus causing either pericardial effusion or life-threatening tamponade. These factors emphasize the importance of an early surgical excision even for extrapericardial locations. This report presents the case of a 16-year-old girl with intrapericardial teratoma who presented with cardiac tamponade which is a rare complication of this rare tumor with only eight cases reported so far beyond infancy. This patient presented with recurrent tamponade, and underwent multiple procedures of pericardiocentesis and developed pyopericardium and polyserositis. This intrapericardial teratoma was not detected by imaging modalities. [ABSTRACT FROM AUTHOR]