Pancreatic ductal adenocarcinoma is an aggressive cancer that interacts with stromal cells to produce a highly inflammatory tumor microenvironment that promotes tumor growth and invasiveness. The precise interplay between tumor and stroma remains poorly understood. TLRs mediate interactions between environmental stimuli and innate immunity and trigger proinflammatory signaling cascades. Our finding that TLR7 expression is upregulated in both epithelial and stromal compartments in human and murine pancreatic cancer led us to postulate that carcinogenesis is dependent on TLR7 signaling. In a mouse model of pancreatic cancer, TLR7 ligation vigorously accelerated tumor progression and induced loss of expression of PTEN, p16, and cyclin D1 and upregulation of p21, p27, p53, c-Myc, SHPTP1, TGF-β, PPARγ, and cyclin B1. Furthermore, TLR7 ligation induced STAT3 activation and interfaced with Notch as well as canonical NF-κB and MAP kinase pathways, but downregulated expression of Notch target genes. Moreover, blockade of TLR7 protected against carcinogenesis. Since pancreatic tumorigenesis requires stromal expansion, we proposed that TLR7 ligation modulates pancreatic cancer by driving stromal inflammation. Accordingly, we found that mice lacking TLR7 exclusively within their inflammatory cells were protected from neoplasia. These data suggest that targeting TLR7 holds promise for treatment of human pancreatic cancer.

Brucellosis is an infectious disease caused by bacteria of the genus Brucella (B.), affecting both animals and humans, causing severe economic loses and severe illness, respectively. The objective of the present study was to determine the seroprevalence and the risk factors associated with caprine, ovine, and bovine brucellosis in selected districts of Punjab, Pakistan. A total of 1083 blood samples were randomly collected from animals (goats = 440, sheep = 203, cows = 206, and buffaloes = 234). Questionnaires were used to collect data on risk factors associated with brucellosis on the sampling day. All samples were initially screened for anti-Brucella antibodies using the rose bengal plate test (RBPT). The seropositive serum samples were confirmed by a quantitative real-time polymerase chain reaction (PCR) assay for the detection of the Brucella genus- and Brucella species-specific DNA (B. abortus and B. melitensis). Univariant and binary logistic regression were used to identify important risk factors of brucellosis. Anti-Brucella antibodies and DNA were detected in 35 (3.23%) serum samples. Thirty-four (97.1%) DNA samples were confirmed as B. melitensis by qRT-PCR. Abortion history and natural mating were found to be potential risk factors. Brucella melitensis was identified as the causative agent of caprine, ovine, and bovine brucellosis in the selected districts of Punjab, Pakistan. Diseased animals may act as a source of infection for other animals. The elimination of positive seroreactors, development of control strategies for brucellosis, and education programs regarding the control of zoonotic disease are highly needed in developing countries like Pakistan.

The urgency for telemedicine is felt during the COVID-19 pandemic which has rendered the world shut by enforcing quarantines and lockdowns. Many developing countries including Pakistan have inadequate telehealth care services that limited access to rural and remote areas. A cross-sectional survey was carried out among medical students i.e., both preclinical and clinical enrolled in various medical colleges from all provinces of Pakistan to determine their Knowledge, Attitude and Perception regarding the use of Telemedicine during the COVID-19 Pandemic. A total of 398 respondents were included in this preliminary survey. Knowledgeable scores were calculated, from a maximum obtainable score of 7. The mean knowledge was found to be significantly associated with age, province, and year of study (p-value < 0.05). Attitude scores were calculated from a maximum obtainable score of 10. All the independent variables failed to reach a significant (p < 0.05) association with the mean attitude of respondents about telemedicine. Perception scores were calculated from a maximum obtainable score of 8. Residents of Khyber Pakhtunkhwa are more likely to know about telemedicine than Balochistan (p = 0.022) on univariate regression. We identified, lack of knowledge and training for telemedicine in medical institutes. It is crucial to assess the knowledge of medical students regarding telemedicine to comprehend, and evaluate their attitude as future doctors who can play a significant role in establishing telemedicine services in the health care system.

Brucellosis is an important zoonotic disease of animals and humans caused by bacteria of the genus Brucella. Brucellae are Gram-negative intracellular bacteria which infect a wide variety of animals including goats, sheep, buffaloes, cows, pigs, and wildlife. The objectives of this study were to determine the seroprevalence and spatial distribution of brucellosis in Central Punjab, Pakistan. A total of 1083 blood samples of goats, sheep, buffaloes, and cows were collected from 38 villages of four districts (Kasur, Faisalabad, Lahore, and Okara) of Punjab, Pakistan, and screened for brucellosis by Rose Bengal Plate test (RBPT) and PCR confirmed. Epidemiological, demographic data and GPS coordinates for every sample were collected. By using interpolation of the Aeronautical Reconnaissance Coverage Geographic Information System (Arc GIS), a surface plot was generated applying inverse distance weight (IDW). It was found that 35 (3.23%) serum samples were positive for brucellosis. In eight (61.5%), six (75%), seven (87.5%), and eight (89%) villages, positive goats, sheep, buffaloes, and cattle were detected, respectively. In general, older animals are more often positive for brucellosis. In goats bucks were more often RBPT positive than females while in sheep, buffaloes, and cattle more females were positive. The spatial distribution of brucellosis shows that it is widely distributed in the western region of the study area in goats and in the South-West region in sheep. Similarly, for buffaloes it is restricted to the south-east and north-west regions, and in cattle brucellosis is present in western region of study area only. Reflected by this study, brucellosis poses a risk for livestock in developing countries due to lack of awareness by officials, owners, and consumers, and control measures are missing. A risk map of brucellosis was generated to develop effective strategies for awareness rising and to improve the quality of control programs in Pakistan.

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Brucellosis is a neglected zoonotic disease of ruminants. It causes severe health problems in humans and significant economic loss. Only a limited number of studies have been conducted in Pakistan to determine the prevalence of human brucellosis and related risk factors. The objectives of the current cross-sectional study were to determine the prevalence of anti-Brucella antibodies in sera collected from symptomatic patients at three hospitals of Abbottabad using a commercial slide agglutination test (SAT) and to determine risk factors for brucellosis for these patients. Five hundred blood samples were collected. A questionnaire was filled in for each patient to obtain information on age, gender, living area, brucellosis associated symptoms, associated risk factors, pregnancy and abortion history. A total of 13.6% (n = 68) patients were found to be SAT positive and in 83.3% (n = 57) of these samples Brucella DNA was detected by genus specific RT-PCR for BCSP-31 gene. Statistical analysis was performed to determine odd ratios, risk ratios, 95% confidence intervals, and p-values. The prevalence of brucellosis by SAT was reported to be higher in women (14.6%, n = 44) than in men (12.1%, n = 24). The age group 25–50 years was found to be at higher risk for brucellosis (14.5%, n = 50) “animal contact” was reported as the main risk factor followed by “consumption of raw animal products.” Out of 131 pregnant women and 21 patients had abortion, the seropositivity of Brucellosis was 9.9% and 23.8%, respectively. The present study reports a striking prevalence of brucellosis among patients including pregnant women at three hospitals of Abbottabad. These findings may foster strategies for controlling human brucellosis at household level, raising of awareness about brucellosis in hospital and family doctors, and finally in setting up an eradication program in the dairy industry.