Pulmonary Spindle Cell Carcinoma: As Rare as a Hen's Teeth.

This case is about a 70-year-old man who presented with symptoms and laboratory reports that indicated differentials toward an infectious disease (pneumonia and tuberculosis). A lung mass was found in his chest X-ray and in the computerized tomography (CT) scan of his thorax. A biopsy was taken from the lung mass, and histopathological examination and immunohistochemical staining of the biopsy were done. The results revealed the presence of spindle cell carcinoma (SpCC) with vimentin and cytokeratin positivity. Spindle cell lung cancer is a rare type of non-small cell lung carcinoma, for which all available research indicates a poor prognosis. Due to the rarity of diagnosis, there is a dearth of information about the epidemiology and overall survival of affected patients.

Evaluation of variations of optic nerve course in relation to posterior paranasal sinuses in MDCT in a tertiary care center of Nepal: a retrospective cross-section study.

Background: The proximity of optic nerves to the posterior paranasal sinuses (PNS) is a critical consideration in preventing optic nerve injuries during functional endoscopic sinus surgery. Methods: A retrospective cross-sectional study was conducted on 367 patients aged 13 years and above. Four radiologists, each with 2-6 years of experience, evaluated computed tomography scans of the PNS and the head of these patients. The optic nerves were classified into four types based on DeLano's classification, and their respective prevalence rates were determined. Additionally, the prevalence of optic nerve dehiscence and pneumatization of the anterior clinoid process was assessed. Results: A total of 734 optic nerves were evaluated and categorized into four groups as per DeLano's classification. The most common type was classified as type 1 optic nerve, representing 65.4% of all optic nerves. Types 2, 3, and 4 optic nerves accounted for 16.9, 8.6, and 9.1%, respectively. The prevalence rates of type 1, type 2, type 3, and type 4 optic nerves were 76.6, 24.5, 12.3, and 14.4%, respectively. Optic nerve dehiscence was observed in 14.3% of cases, with a prevalence of 21.2% in the study. Type 3 optic nerves were most commonly associated with dehiscence, with 49.2% of them showing dehiscence in their course through the ethmoid or sphenoid sinus. The prevalence of pneumatization of the anterior clinoid process in the study population was 28.3%, with type 3 optic nerves being the most frequently associated. Conclusion: An understanding of the relationship between optic nerves and posterior PNS, as well as awareness of optic nerve dehiscence, is essential in preventing injuries during sinus surgeries. Type 1 optic nerve predominates among Nepalese patients visiting our hospital.

An Overview of Bacteria-Mediated Heavy Metal Bioremediation Strategies.

Contamination-free groundwater is considered a good source of potable water. Even in the twenty-first century, over 90 percent of the population is reliant on groundwater resources for their lives. Groundwater influences the economical state, industrial development, ecological system, and agricultural and global health conditions worldwide. However, different natural and artificial processes are gradually polluting groundwater and drinking water systems throughout the world. Toxic metalloids are one of the major sources that pollute the water system. In this review work, we have collected and analyzed information on metal-resistant bacteria along with their genetic information and remediation mechanisms of twenty different metal ions [arsenic (As), mercury (Hg), lead (Pb), chromium (Cr), iron (Fe), copper (Cu), cadmium (Cd), palladium (Pd), zinc (Zn), cobalt (Co), antimony (Sb), gold (Au), silver (Ag), platinum (Pt), selenium (Se), manganese (Mn), molybdenum (Mo), nickel (Ni), tungsten (W), and uranium (U)]. We have surveyed the scientific information available on bacteria-mediated bioremediation of various metals and presented the data with responsible genes and proteins that contribute to bioremediation, bioaccumulation, and biosorption mechanisms. Knowledge of the genes responsible and self-defense mechanisms of diverse metal-resistance bacteria would help us to engineer processes involving multi-metal-resistant bacteria that may reduce metal toxicity in the environment.

Does foreign aid affect innovation and institutional quality in middle-income countries?

In this study, we explore the dynamics between innovation, institutional quality, and foreign-aid flows in middle-income countries. Using an appropriate econometric model, we investigate the links between these variables in 79 middle-income countries (MICs) over 2005-2020. The results from our study show that foreign aid, institutional quality, and innovation have strong endogenous relationships. The short-run outcomes show that innovation Granger-causes institutional quality; foreign aid Granger-causes innovation; and quality of institutions Granger-causes foreign aid. The long-run outcomes indicate that institutional quality and innovation significantly affect the flow of foreign aid to the MICs. These results indicate that policy-makers in both foreign aid donor and recipient countries should pursue appropriate policies on foreign aid, quality of institutions, and innovation. For instance, in the short run, planners and evaluators in donor countries can direct their aid to MICs that have persistent challenges in improving their institutions and enhancing their innovative capabilities. In the long run, recipient countries ought to recognize that their institutional quality and innovation have a considerable impact on the inflows of foreign aid to their countries.

Fine-tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis.

Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvß3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells, noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.

The Effects of Trash, Residential Biofuel, and Open Biomass Burning Emissions on Local and Transported PM2.5 and Its Attributed Mortality in Africa.

Long-term exposure to ambient fine particulate matter (PM2.5) is the second leading risk factor of premature death in Sub-Saharan Africa. We use GEOS-Chem to quantify the effects of (a) trash burning, (b) residential solid-fuel burning, and (c) open biomass burning (BB) (i.e., landscape fires) on ambient PM2.5 and PM2.5-attributable mortality in Africa. Using a series of sensitivity simulations, we excluded each of the three combustion sources in each of five African regions. We estimate that in 2017 emissions from these three combustion sources within Africa increased global ambient PM2.5 by 2%, leading to 203,000 (95% confidence interval: 133,000-259,000) premature mortalities yr-1 globally and 167,000 premature mortalities yr-1 in Africa. BB contributes more ambient PM2.5-related premature mortalities per year (63%) than residential solid-fuel burning (29%) and trash burning (8%). Open BB in Central Africa leads to the largest number of PM2.5-attributed mortalities inside the region, while trash burning in North Africa and residential solid-fuel burning in West Africa contribute the most regional mortalities for each source. Overall, Africa has a unique ambient air pollution profile because natural sources, such as windblown dust and BB, contribute strongly to ambient PM2.5 levels and PM2.5-related mortality. Air pollution policies may need to focus on taking preventative measures to avoid exposure to ambient PM2.5 from these less-controllable sources.

Giant Bullous Emphysema Mimicking Spontaneous Pneumothorax.

Emphysema is a progressive and degenerative lung disease that most commonly occurs due to many years of smoking or exposure to smoke and irritants. It is also seen in the congenital absence of the alpha-1-antitrypsin enzyme. Bullous emphysema is an advanced stage of the disease where strictures of the bronchi permit the inspired air to enter the bronchi but close on expiration, causing air retention and alveolar dilation, destruction, and atrophy. Multiple small bullae coalesce to form a giant bulla (defined as occupying more than one-third of the hemithorax), which causes respiratory symptoms and mediastinal shifting and leads to a poor general condition of the patient. Here, we present the cases of two patients diagnosed with bullous emphysema who presented within three months of each other. This article details the similarities and differences in the approach to both cases and the learning experience from these presentations, especially in acute symptomatology. Bullous emphysema is usually confused with a pneumothorax on a simple chest X-ray; hence, it is imperative to look for the lung margins and confirm the diagnosis using computed tomography of the thorax.

Prokaryotic ncRNAs: Master regulators of gene expression.

ncRNA plays a very pivotal role in various biological activities ranging from gene regulation to controlling important developmental networks. It is imperative to note that this small molecule is not only present in all three domains of cellular life, but is an important modulator of gene regulation too in all these domains. In this review, we discussed various aspects of ncRNA biology, especially their role in bacteria. The last two decades of scientific research have proved that this molecule plays an important role in the modulation of various regulatory pathways in bacteria including the adaptive immune system and gene regulation. It is also very surprising to note that this small molecule is also employed in various processes related to the pathogenicity of virulent microorganisms.

Unilateral Choroidal Granuloma and a Pupillary Abnormality in a Case of Miliary Tuberculosis: A Dilemma for the Physician.

A young woman presented to the emergency with acute paraplegia and vision loss. She was diagnosed two months ago as a case of miliary tuberculosis with involvement of the chest and brain and therefore was on anti-tuberculosis treatment (ATT). She developed a decrease in vision and her treating physician suspecting optic neuropathy altered the regimen so as to omit Ethambutol and replaced it with Streptomycin. This treatment could not be continued with the advent of the COVID-19 pandemic as it required a hospital visit. On admission, she gave a history of inconsistent treatment and the ophthalmology evaluation showed decreased vision in the left eye, a relative afferent pupillary defect (RAPD), and a large solitary choroidal tubercle at the posterior pole of the same eye. The right eye was normal. On discussion with the treating physician, the standard four-drug ATT was reinstituted. Through our case report, we wish to highlight a challenging situation wherein the vision loss and pupillary abnormality with a background of ATT led to the change of treatment that would have required either daily hospital visits or other arrangements to be made to provide the same at home. This modified regimen not only proved to be challenging for the patient and caregivers but also may have played a role in the newer onset of further complications secondary to an irregular treatment regime.

A 17-year-old indwelling ureteral stent with large vesical calculus at one end: The tombstone of a forgotten Double "J" stent.

Objective: To highlight the presentation and management of a 17-year-old forgotten ureteral stent with a large vesical calculus at one end, a very rare yet devastating complication of ureteral stenting. Case Presentation: A 65-year-old gentleman presented with complaints of lower urinary tract symptoms for two years with a history of ureterolithotomy done 17 years ago. Imaging revealed a forgotten ureteral stent embedded in a large vesical calculus. He underwent a percutaneous cystolithotomy with removal of the forgotten stent. Conclusion: DJ stent is commonly used in urologic practice. It is a double-edged sword as it can lead to severe morbidity in patients who have forgotten stent. Knowledge of DJ stent-related complications and need of timely removal will help primary care physician in providing better health care. Proper counselling of patients before and after the placement of stent and maintenance of stent registries play a major role in avoiding this dreadful complication.

Tunnelling a calcified total occlusion.

Among the complex and high-risk coronary intervention cases, a calcified total occlusion of coronary artery poses a great challenge. We came across a 48 years old male who had calcified total occlusion of the right coronary artery. The chronic total occlusion was crossed using Nic-Nano balloon and the calcific plaque was modified using intravascular lithotripsy as an alternative technique to rotational atherectomy which we felt as an evolving alternative approach to treat the calcified total occlusion.

Integrative Bioinformatics Approaches Indicate a Particular Pattern of Some SARS-CoV-2 and Non-SARS-CoV-2 Proteins.

Pattern recognition plays a critical role in integrative bioinformatics to determine the structural patterns of proteins of viruses such as SARS-CoV-2. This study identifies the pattern of SARS-CoV-2 proteins to depict the structure-function relationships of the protein alphabets of SARS-CoV-2 and COVID-19. The assembly enumeration algorithm, Anisotropic Network Model, Gaussian Network Model, Markovian Stochastic Model, and image comparison protein-like alphabets were used. The distance score was the lowest with 22 for "I" and highest with 40 for "9". For post-processing and decision, two protein alphabets "C" (PDB ID: 6XC3) and "S" (PDB ID: 7OYG) were evaluated to understand the structural, functional, and evolutionary relationships, and we found uniqueness in the functionality of proteins. Here, models were constructed using "SARS-CoV-2 proteins" (12 numbers) and "non-SARS-CoV-2 proteins" (14 numbers) to create two words, "SARS-CoV-2" and "COVID-19". Similarly, we developed two slogans: "Vaccinate the world against COVID-19" and "Say no to SARS-CoV-2", which were made with the proteins structure. It might generate vaccine-related interest to broad reader categories. Finally, the evolutionary process appears to enhance the protein structure smoothly to provide suitable functionality shaped by natural selection.

Genome structure and genetic diversity in the Ebola virus.

Ebola is a deadly pathogen responsible for Ebola virus disease, first came to prominence in the year 1976. This rapidly evolving virus imposed a serious threat to the human population in the last few decades and also continues to be a probable threat to our race. A better understanding of the virus in terms of its genomic structure is very much needed to develop an effective antiviral therapy against this deadly pathogen. Complete knowledge of its genomic structure and variations will help us and the entire scientific community to design effective therapy in terms of either vaccine development or the development of proper antiviral medicine.

Modified "parachute technique" of partial penectomy: A penile preservation surgery for carcinoma penis.

Carcinoma penis is a rare malignancy which mostly occurs after the sixth decade of life. It is managed surgically and partial penectomy is the most common procedure done in carcinoma involving the distal penis. Partial penectomy provides the opportunity of preservation of sexual function and enables the patient to micturate in standing position. The conventional technique of neourethra creation in partial penectomy is slitting the urethra dorsally. We propose an alternative approach to neourethra formation. Technique involves ventral slitting of the urethra followed by suturing which begins at the ventral aspect and continued in a parachute fashion toward the dorsal end. This new technique will help primary physicians and surgeons in providing better surgical results in caring for patients with carcinoma penis.

Ongoing Clinical Trials of Vaccines to Fight against COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.

SARS-CoV-2 and other human coronaviruses: Mapping of protease recognition sites, antigenic variation of spike protein and their grouping through molecular phylogenetics.

In recent years, a total of seven human pathogenic coronaviruses (HCoVs) strains were identified, i.e., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Here, we performed an analysis of the protease recognition sites and antigenic variation of the S-protein of these HCoVs. We showed tissue-specific expression pattern, functions, and a number of recognition sites of proteases in S-proteins from seven strains of HCoVs. In the case of SARS-CoV-2, we found two new protease recognition sites, each of calpain-2, pepsin-A, and caspase-8, and one new protease recognition site each of caspase-6, caspase-3, and furin. Our antigenic mapping study of the S-protein of these HCoVs showed that the SARS-CoV-2 virus strain has the most potent antigenic epitopes (highest antigenicity score with maximum numbers of epitope regions). Additionally, the other six strains of HCoVs show common antigenic epitopes (both B-cell and T-cell), with low antigenicity scores compared to SARS-CoV-2. We suggest that the molecular evolution of structural proteins of human CoV can be classified, such as (i) HCoV-NL63 and HCoV-229E, (ii) SARS-CoV-2, and SARS-CoV and (iii) HCoV-OC43 and HCoV-HKU1. In conclusion, we can presume that our study might help to prepare the interventions for the possible HCoVs outbreaks in the future.

Rare Presentation of Tuberculosis Mimicking Malignancy.

Tuberculosis is one of the most common infectious diseases that has a varied presentation and can affect most of the organs of the body. Differentiating disseminated tuberculosis with minimal symptoms from malignancy is difficult and makes the diagnosis challenging. No single test can be earmarked to diagnose tuberculosis and multiple investigations are mostly required. Here, we would like to discuss a rare case of a young male with mild symptoms who, on initial investigations, was provisionally diagnosed as having a metastatic disease, but detailed investigations proved it to be a case of disseminated tuberculosis. Through this case, we learn that radiological images alone cannot help in diagnosing even a common disease like tuberculosis. A complete workup helped in differentiating malignancy from tuberculosis in this mildly symptomatic patient.

Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. METHODS: PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. RESULTS: A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). CONCLUSIONS: Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.