Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole.

Intracellular membrane fusion is mediated by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Reports also suggest that Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. Salmonella containing vacuole (SCV) harbours recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis remains unclear. Upon knockdown of STX3, we observed a reduction in bacterial proliferation, which is concomitantly restored upon the overexpression of STX3. Live-cell imaging of Salmonella-infected cells showed that STX3 localises to the SCV membranes and thus might help in the fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found the interaction STX3-SCV was abrogated when we infected with SPI-2 encoded Type 3 secretion system (T3SS) apparatus mutant (STM ∆ssaV) but not with SPI-1 encoded T3SS apparatus mutant (STM ∆invC). These observations were also consistent in the mice model of Salmonella infection. Together, these results shed light on the effector molecules secreted through T3SS encoded by SPI-2, possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and help to maintain a single bacterium per vacuole.

Metastatic melanoma in the breast and axilla: A case report.

Metastatic melanoma of the breast is rare, and demonstrates nonspecific imaging findings which may overlap with both benign and malignant pathology.1-3 Immunohistochemical stains are important to confirm the diagnosis, particularly combining S100, a sensitive marker for melanoma, with more specific tumor markers such as Melan-A and HMB-45, and lack of cytokeratin staining.4-7 We present a case of a 64-year-old female who presented for diagnostic imaging of a palpable abnormality in her right breast, with medical history notable for previously excised cutaneous melanoma, recent COVID-19 vaccination, and significant family history of breast cancer. Diagnostic mammogram of the right breast demonstrated a circumscribed mass in the lower inner quadrant corresponding to the area of palpable concern, as well as an additional non-palpable circumscribed mass in the lower inner quadrant. Targeted right breast ultrasound demonstrated corresponding circumscribed cystic versus solid masses as well as a morphologically abnormal right axillary lymph node. Pathologic results after tissue sampling of the two right breast masses and right axillary lymph node all yielded metastatic melanoma.

Computational fluid dynamics-based disease transmission modeling of SARS-CoV-2 Intensive Care Unit.

Covid-19 has become one of the most severe diseases causing acute respiratory problems and has killed millions of people worldwide. It was declared as the ongoing pandemic by the World Health Organization. It is an infectious virus which can be transmitted by sneezing, coughing and exhalation of air by any infected person. There are certain places having high chances of becoming contaminated like hospital rooms. In this context, we studied the transmission of Covid-19 particles in an ICU room. We have considered the combined effect of both of air-conditioning (AC) and ceiling fan in the room. The infected person can transmit the disease when under influence of fan and AC. The work highlights the flow of aerosol particles considering the combined effect as well as the individual effects of fan and AC. The results also emphasized that the aerosol particle flow have a promising application in sanitizing the room.

Unilateral axillary adenopathy in the setting of COVID-19 vaccine: Follow-up.

With the Pfizer-BioNTech, Moderna, and now Johnson and Johnson COVID-19 vaccines readily available to the general population, the appearance of vaccine-induced axillary adenopathy on imaging has become more prevalent. We are presenting follow up to the first reported four cases of vaccine induced unilateral axillary adenopathy on imaging to our knowledge, which demonstrate expected self-resolving adenopathy. Our hope is that by providing this follow-up and reviewing current management guidelines, clinicians as well as patients will appreciate that this is an expected, benign, and self-resolving finding. In addition, we hope to quell any vaccine hesitancy brought about by recent mainstream media attention to this topic and ultimately empower patients to receive both the COVID-19 vaccine and undergo routine screening mammography, as both are vital to their health.

Merkel cell carcinoma of the breast: A case report.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 20181). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 20142). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 20181). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.

Unilateral axillary Adenopathy in the setting of COVID-19 vaccine.

With the recent U.S. Food and Drug Administration (FDA)-approval and rollout of the Pfizer-BioNTech and Moderna COVID-19 vaccines, it is important for radiologists to consider recent COVID-19 vaccination history as a possible differential diagnosis for patients with unilateral axillary adenopathy. Hyperplastic axillary nodes can be seen on sonography after any vaccination but are more common after a vaccine that evokes a strong immune response, such as the COVID-19 vaccine. As the differential of unilateral axillary adenopathy includes breast malignancy, it is crucial to both thoroughly evaluate the breast for primary malignancy and to elicit history of recent vaccination. As COVID-19 vaccines will soon be available to a larger patient population, radiologists should be familiar with the imaging features of COVID-19 vaccine induced hyperplastic adenopathy and its inclusion in a differential for unilateral axillary adenopathy. Short-term follow-up for unilateral axillary adenopathy in the setting of recent COVID-19 vaccination is an appropriate recommendation, in lieu of immediately performing potentially unnecessary and costly axillary lymph node biopsies.

Multiorgan metastatic invasive lobular Carcinoma initially presenting as diplopia.

We present an interesting case of biopsy-proven multiorgan metastatic invasive lobular carcinoma to the orbits and kidney, initially presenting in a 76-year-old woman with diplopia. Invasive lobular carcinoma is a less common subtype of breast cancer and is often difficult to detect on imaging with an unusual metastatic pattern when compared to invasive ductal carcinoma. Metastatic invasive lobular carcinoma most frequently involves the orbits, ovaries, gastrointestinal tract, retroperitoneum and bone. Disease involving these organ systems detected on imaging should raise concern for metastatic disease when appropriate.

Complex Solid and Cystic Breast Cancer: A Series of Six Case Reports.

A cyst in the breast containing a thick wall, internal septations, or a solid intracystic component is defined as a complex solid and cystic breast mass. These lesions carry a malignant potential between 23-31% and thus require further evaluation with biopsy [1]. We report six cases in which patients were found to have a complex solid and cystic mass, all of which were proven to be malignant breast cancers of varying etiologies. We also review the literature on malignant etiologies of complex solid and cystic breast masses, including their clinical presentation, work-up, histopathologic and immunochemistry findings, treatment, and prognosis.

Invasive Colloid Carcinoma and the role of Ki-67 and HER2 - Two case reports.

Mucinous carcinoma (also termed colloid carcinoma) of the breast accounts for 1%-6% of all breast cancer and is considered to have a good relative prognosis. The most common mammographic appearance of pure mucinous carcinoma is a high-density mass with circumscribed margins and on sonographic examination an isoechoic round mass with circumscribed margins. We report 2 cases of invasive mucinous carcinoma, in which one patient showed an intermediate recurrence risk based on Ki-67 and human epidermal growth factor receptor 2 negativity, while the other showed a low Ki-67 recurrence risk and human epidermal growth factor receptor 2 positive. We also review the literature on Ki-67 and human epidermal growth factor receptor 2 and explore the roles of these molecular markers in mucinous carcinomas.

Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy.

We compared thrombophilia in 67 cases (59 men and 8 women) with thrombotic events after starting testosterone therapy (TT) versus 111 patient controls having unprovoked venous thrombotic events without TT. In the 67 patients, thrombosis (47 deep venous thrombosis-pulmonary embolism, 16 osteonecrosis, and 4 ocular thrombosis) occurred 6 months (median) after starting TT. Cases differed from controls for factor V Leiden heterozygosity (16 of the 67 [24%] vs 13 [12%] of the 111, P = .038) and for lupus anticoagulant (9 [14%] of the 64 vs 4 [4%] of the 106, P = .019). After a first thrombotic event and continuing TT, 11 cases had a second thrombotic event, despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third thrombosis. Screening for thrombophilia before starting TT should identify men and women at high risk for thrombotic events with an adverse risk-benefit ratio for TT. When TT is given to patients with familial and acquired thrombophilia, thrombosis may occur and recur in thrombophilic men despite anticoagulation.

Influence of medical comorbidities on the presentation and outcomes of stage I-III non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer presentation, treatment, and outcomes vary widely according to socioeconomic factors and other patient characteristics. To determine whether medical comorbidities account for these observations, we incorporated a validated medical comorbidity index into an analysis of patients diagnosed with stage I to III NSCLC. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive patients diagnosed with stage I to III NSCLC. Demographic, tumor, and comorbidity data were obtained from hospital tumor registries and individual patient records. The association between variables was assessed using multivariate logistic regression and survival analysis. RESULTS: A total of 454 patients met criteria for analysis. The median age was 65 years, and 51% were men. Individuals with a higher Charlson Comorbidity Index (CCI) were significantly more likely to present with early stage (stage I-II) NSCLC than were patients with lower CCI (odds ratio, 1.72; 95% confidence interval, 1.14-2.63; P = .01), although this association lost statistical significance (P = .21) in a multivariate model. In multivariate logistic regression, overall survival remained associated with all variables: age, sex, race, insurance type, stage, histology, and CCI (P = .0007). The CCI was associated with survival for patients with early stage (P = .02) and locally advanced (P = .02) disease. CONCLUSION: In this cohort of patients with stage I to III NSCLC, increasing comorbidity burden had a nonsignificant association with diagnosis at earlier disease stage. Although comorbidity burden was significantly associated with outcome for early stage and locally advanced disease, it did not account for survival differences based on multiple other patient and disease characteristics.

Russian Old Believers: genetic consequences of their persecution and exile, as shown by mitochondrial DNA evidence.

In 1653, the Patriarch Nikon modified liturgical practices to bring the Russian Orthodox Church in line with those of the Eastern (Greek) Orthodox Church, from which it had split 200 years earlier. The Old Believers (staroveri) rejected these changes and continued to worship using the earlier practices. These actions resulted in their persecution by the Russian Orthodox Church, which forced them into exile across Siberia. Given their history, we investigate whether populations of Old Believers have diverged genetically from other Slavic populations as a result of their isolation. We also examine whether the three Old Believer populations analyzed in this study are part of a single gene pool (founder population) or are instead derived from heterogeneous sources. As part of this analysis, we survey the mitochondrial DNAs (mtDNAs) of 189 Russian Old Believer individuals from three populations in Siberia and 201 ethnic Russians from different parts of Siberia for phylogenetically informative mutations in the coding and noncoding regions. Our results indicate that the Old Believers have not significantly diverged genetically from other Slavic populations over the 200-300 years of their isolation in Siberia. However, they do show some unique patterns of mtDNA variation relative to other Slavic groups, such as a high frequency of subhaplogroup U4, a surprisingly low frequency of haplogroup H, and low frequencies of the rare East Eurasian subhaplogroup D5.