The immune phenotype of perinatal anxiety in an anxiety-focused behavioral intervention program in Pakistan.

BACKGROUND: Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms-the Happy Mother - Healthy Baby (HMHB) study in Rawalpindi, Pakistan. MATERIALS AND METHODS: Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale - HADS -using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded. RESULTS: K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (ß = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (ß = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (ß = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA). CONCLUSION: Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861).

Silicosis, asbestosis, and pulmonary fibrosis in Ontario, Canada from 1996 to 2019.

BACKGROUND: Silicosis is a fibrotic lung disease caused by exposure to respirable crystalline silica. Historically, silicosis was common among miners and other professions in the 20th century, and in recent decades has re-emerged in coal mining and appeared in new workplaces, including the manufacture of distressed jeans and artificial stone countertops. METHODS: Physician billing data for the province of Ontario between 1992 and 2019 were analyzed across six time-periods (1993-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2019). The case definition was two or more billing records within 24 months with a silicosis diagnosis code (ICD-9 502, ICD-10 J62). Cases from 1993 to 1995 were excluded as prevalent cases. Crude incidence rates per 100,000 persons were calculated by time-period, age, sex, and region. Analyses were repeated in parallel for pulmonary fibrosis (PF) (ICD-9 515, ICD-10 J84) and asbestosis (ICD-9 501; ICD-10 J61). RESULTS: From 1996 to 2019, 444 cases of silicosis, 2719 cases of asbestosis and 59,228 cases of PF were identified. Silicosis rates decreased from 0.42 cases per 100,000 in 1996-2000 to 0.06 per 100,000 people in 2016-2019. A similar trend was observed for asbestosis (1.66 to 0.51 per 100,000 persons) but the incidence rate of PF increased from 11.6 to 33.9 per 100,000 persons. Incidence rates for all outcomes were higher among men and older adults. CONCLUSIONS: A decreasing incidence of silicosis was observed in this analysis. However, the incidence of PF increased, consistent with findings from other jurisdictions. While cases of silicosis have been recorded among artificial stone workers in Ontario these cases do not seem to have impacted the population rates thus far. Ongoing, periodic surveillance of occupational diseases is helpful for tracking population-level trends over time.

"Aberrant sialylation plays a significant role in oral squamous cell carcinoma progression".

OBJECTIVE: Aberrant glycosylation, mainly sialylation and fucosylation, is recently considered as a major hallmark of cancer. Aberrant sialylation has long been associated with various neoplastic diseases. However, role of aberrant sialylation in oral cancer is still in its infancy. The present study aimed to examine mRNA expressions of α-2, 3, α-2, 6 sialyltransferase (ST) families and sialidase in 160 human oral cancer tissues. METHODS: mRNA expression of ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL6, ST6GAL1, and neuraminidase 3 (NEU3) was analyzed by RT-qPCR in 80 paired malignant and adjacent normal tissues from oral cancer patients. RESULTS: The results indicated significant (P ≤ .05) down-regulation of various STs (ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL6, and ST6GAL1) and sialidases (NEU3) in malignant tissues as compared to adjacent normal tissues. Higher mRNA levels of ST3GAL2 and ST3GAL3 were significantly associated with advanced stage of the disease, lymph node involvement, and perineural invasion, which denote their role in progression and metastasis of oral cancer. Present study also revealed altered sialylation patterns according to anatomical site of the disease and tobacco habit. CONCLUSION: The study demonstrated significant role of elevated mRNA levels of ST3GAL2 and ST3GAL3 in disease progression and metastasis of oral carcinoma.

Transthoracic echocardiographic detection of pulmonary valve involvement in Löeffler's endocarditis.

We are describing pulmonary valve involvement with thickening and stenosis detected by two-dimensional transthoracic echocardiography in an adult presenting with Löeffler's endocarditis. To our knowledge, this has not been described previously. Complete regression of the lesions occurred with corticosteroid therapy. Tricuspid valve thickening and stenosis and thickening and thrombus formation in the right ventricle also present initially disappeared completely with therapy.

Two- and three-dimensional transthoracic echocardiography in the assessment of acquired ascending aortic aneurysm to pulmonary artery fistula.

Aorta to pulmonary artery fistula is an uncommon and potentially fatal condition. This case is of a 48-year-old Caucasian male with congestive heart failure and multiple aortic valve replacement surgeries who presented with an acquired ascending aortic aneurysm to pulmonary artery fistula diagnosed using two-dimensional transthoracic echocardiography via nonstandard imaging windows. Three-dimensional transthoracic echocardiography using live/real time three-dimensional color Doppler was used to assess the size of the opening of the fistula, providing additional value. This patient was surgically managed and is doing well 8 months postoperation.

Cardiac device-related invasive aspergilloma assessed by live/real time three-dimensional transthoracic echocardiography.

Cardiac device-related infection caused by Aspergillus species is a rare finding associated with high mortality. Prompt recognition and treatment is imperative, but difficult as blood cultures are often negative and diagnosis requires a high index of suspicion. Live/real time three-dimensional transthoracic echocardiography (3DTTE) provides incremental knowledge in the characterization of valvular vegetations. Here, we provide a detailed description of an invasive cardiac device-related infection caused by Aspergillus fumigatus using 3DTTE. Findings described here highlight the role for 3DTTE in the prompt diagnosis of invasive cardiac Aspergillus infections as well as surgical planning in such cases.

Incremental value of three-dimensional transesophageal echocardiography over two-dimensional transesophageal echocardiography in the assessment of Lambl's excrescences and nodules of Arantius on the aortic valve.

In this retrospective study, we identified 7 cases where Lambl's excrescences were identified by two-dimensional transesophageal echocardiography (2DTEE) and also had live/real time three-dimensional transesophageal echocardiography (3DTEE) studies available for comparison. We subsequently assessed them for the presence of Lambl's excrescences (LE) and nodules of Arantius (NA) on the aortic valve. After their identification, we qualitatively and quantitatively organized our findings by number, cusp location, measurements, and orientation if applicable. A greater number of LE was found by 3DTEE than 2DTEE (19 vs. 11, respectively). In all 3DTEE studies, their cusp attachment site, their x-, y-, and z-axis measurements, and orientation were clearly visualized and described. Only 3DTEE studies provided confident visualization of the cusp attachment sites. Similarly, a greater number of NA was found by 3DTEE than 2DTEE (21 vs. 5, respectively). The triad of NA was visualized in all 3DTEE studies and each was described using its x-, y-, and z- axis measurements. Only three 2DTEE studies provided reliable identification of the NA. In conclusion, we present further evidence of the incremental value of 3DTEE over 2DTEE in the qualitative and quantitative assessment of cardiac structures including LE and NA on the aortic valve.

Altered mRNA Expression of Fucosyltransferases and Fucosidase Predicts Prognosis in Human Oral Carcinoma.

Aberrant protein glycosylation is known to be associated with the development of various cancers. Although fucosylation is essential for normal biological functions, alterations in fucosylation are strongly implicated in cancer and increasing metastatic potential. Altered fucosyltarnsferases (FUTs) and fucosidases are found to be involved in many types of malignancies. In this study, we examined the mRNA expressions of fucosidase (FUCA1) and FUTs (FUTs (FUT3, FUT4, FUT5, FUT6, FUT8) in human oral cancer tissues. All FUTs and FUCA1 were significantly (P ≤0.05) down-regulated in malignant tissues in comparison with their adjacent normal tissues. The relationship between the clinicopathological parameters and the expression of FUTs and FUCA1 revealed that higher mRNA levels of FUT4, FUT5, and FUT8 and lower levels of FUT3 were associated with progression of disease and lymph node metastasis in oral carcinoma indicating their role in oral cancer progression. Collectively, results suggest that elevated mRNA levels of FUT4, FUT5 and FUT8 may be used as worst prognostic indicators for oral carcinoma.

Curbing the Deregulation of Glycosylation in Tongue Carcinoma Cells with Natural Compounds.

BACKGROUND: Aberrant glycosylation has been recently considered as a major hallmark of cancer. Furthermore, we have reported that aberrant glycosylation, mainly sialylation and fucosylation, plays a major role in oral cancer progression and metastasis. OBJECTIVE: In the present study, we evaluated the role of tobacco compounds (4-NQO, NNK, Benzopyrene), natural compounds (Curcumin, Butein and Piceatannol) and commonly used chemotherapeutic compound (Cisplatin) on sialylation and fucosylation transcript levels in the tongue cancer cell line (SAS). METHODS: The SAS cells were treated with the tobacco compounds, natural compounds and Cisplatin after obtaining their IC50 values using MTT assay. After 24 hr treatment of the compounds, RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed for mRNA expression of glycosylation transcripts. RESULTS: The treatment of tobacco compounds on the SAS cells resulted in increased mRNA levels of ST3GAL1, NEU3, FUT5 and FUT6 in a dose-dependent manner. The treatment of Curcumin and Butein resulted in lower mRNA levels of FUT8, whereas dose-dependent higher mRNA levels of FUT3 were also observed after the treatment of Curcumin. SAS cells exhibited a dose-dependent decrease in ST3GAL2, FUT5 and FUT8 mRNA after Piceatannol treatment. Furthermore, Cisplatin treatment on the SAS cells resulted in increased mRNA levels of FUT3 as the concentration increased from 100 µM to 200 µM. While, treatment of Cisplatin resulted in decreased mRNA levels of ST3GAL2, ST3GAL3, FUT5 and FUT8 in a dose-dependent manner. All together, the data revealed Piceatannol as a potent synergistic for Cisplatin to target the altered glycosylation for better treatment management of tongue carcinoma. CONCLUSION: The study provides a normal approach of targeting aberrant glycosylation with natural compounds, which may open the possibility of newer therapeutic strategies using natural compounds alone or in combination with other conventional therapies.

Human papillomavirus: footprints in the population of western India.

OBJECTIVES: Cancer is a multi-factorial disease, with various intrinsic and environmental factors contributing to its occurrence. Human papillomavirus (HPV) has been associated with the occurrence of many cancers. India severely suffers from 3 HPV-associated cancers (cervical cancer, oral cancer, and oropharyngeal cancer). Hence, the present study aimed to evaluate the HPV burden in these 3 cancers among patients from the western region of India. METHODS: DNA was isolated from samples from 400 cervical cancer, 127 oral cancer, and 75 oropharyngeal cancer patients. Polymerase chain reaction was performed using degenerate primers for HPV infection. RESULTS: Overall, HPV infection was observed in 87% of cervical cancer cases, 12.5% of oral cancer cases, and 26.7% of oropharyngeal cancer cases when analyzed with a cumulative detection method using the MY 09/11, GP 5+/6+, and CP I/II primer sets. CONCLUSIONS: A significant prevalence of HPV infection was detected in all 3 cancers using the degenerate primer sets. This finding implies that testing for HPV infection using multiple primer sets is crucial for determining its actual prevalence in various malignancies.

ParA encoded on chromosome II of Deinococcus radiodurans binds to nucleoid and inhibits cell division in Escherichia coli.

Bacterial genome segregation and cell division has been studied mostly in bacteria harbouring single circular chromosome and low-copy plasmids. Deinococcus radiodurans, a radiation-resistant bacterium, harbours multipartite genome system. Chromosome I encodes majority of the functions required for normal growth while other replicons encode mostly the proteins involved in secondary functions. Here, we report the characterization of putative P-loop ATPase (ParA2) encoded on chromosome II of D. radiodurans. Recombinant ParA2 was found to be a DNA-binding ATPase. E. coli cells expressing ParA2 showed cell division inhibition and mislocalization of FtsZ-YFP and those expressing ParA2-CFP showed multiple CFP foci formation on the nucleoid. Although, in trans expression of ParA2 failed to complement SlmA loss per se, it could induce unequal cell division in slmAminCDE double mutant. These results suggested that ParA2 is a nucleoid-binding protein, which could inhibits cell division in E. coli by affecting the correct localization of FtsZ and thereby cytokinesis. Helping slmAminCDE mutant to produce minicells, a phenotype associated with mutations in the 'Min' proteins, further indicated the possibility of ParA2 regulating cell division by bringing nucleoid compaction at the vicinity of septum growth.