Identification and isolation of Brucella suis virulence genes involved in resistance to the human innate immune system

Brucella strains are facultative intracellular pathogens that induce chronic diseases in humans and animals. This observation implies that Brucella subverts innate and specific immune responses of the host to develop its full virulence. Deciphering the genes involved in the subversion of the immune system is of primary importance for understanding the virulence of the bacteria, for understanding the pathogenic consequences of infection, and for designing an efficient vaccine. We have developed an in vitro system involving human macrophages infected by Brucella suis and activated syngeneic gamma9delta2 T lymphocytes. Under these conditions, multiplication of B. suis inside macrophages is only slightly reduced. To identify the genes responsible for this reduced sensitivity, we screened a library of 2,000 clones of transposon-mutated B. suis. For rapid and quantitative analysis of the multiplication of the bacteria, we describe a simple method based on Alamar blue reduction, which is compatible with screening a large library. By comparing multiplication inside macrophages alone and multiplication inside macrophages with activated gamma9delta2 T cells, we identified four genes of B. suis that were necessary to resist to the action of the gamma9delta2 T cells. The putative functions of these genes are discussed in order to propose possible explanations for understanding their exact role in the subversion of innate immunity.     

Adjunctive lacosamide for focal epilepsy: an open‐label trial evaluating the impact of flexible titration and dosing on safety and seizure outcomes

Aims. To evaluate the safety and effectiveness of lacosamide in a real‐life setting with the use of a flexible dose titration schedule and individualised maintenance doses up to the maximum approved dose of 400 mg/day. Methods. Adults with a diagnosis of focal seizures, with or without secondary generalization, were enrolled in this open‐label Phase IV trial (NCT01235403). Lacosamide was initiated at 100 mg/day (50 mg bid) and uptitrated over a 12‐week period to 200, 300 or 400 mg/day, based on safety and seizure control. Although dose increases were to be in increments of 100 mg/day, intermediate doses were permitted at each escalation step for one week for patients known to be particularly sensitive to starting new AEDs. After receiving a stable, effective dose for three weeks, patients entered the 12‐week maintenance period. Primary outcomes were incidence of treatment‐emergent adverse events (TEAEs) and withdrawal due to TEAEs. Seizure outcomes, all secondary, were median focal seizure frequency, ≥50% reduction in focal seizure frequency, and seizure freedom. Results. One hundred patients with a mean age of 44 years were enrolled and 74 completed the trial. The incidence of TEAEs was 64.0% (n=100), with the most frequently reported (≥5% of patients) being dizziness, headache, and asthenia. Fourteen patients withdrew due to TEAEs, most frequently due to dizziness (six patients; 6.0%), vomiting (two patients; 2%), and tremor (two patients; 2%). Among patients with baseline and maintenance phase seizure data (n=75), median reduction in focal seizure frequency from baseline was 69.7% and the ≥50% responder rate was 69.3%. Among 74 patients who completed the maintenance phase, 21 (28.4%) were seizure‐free. Conclusion. Flexible lacosamide dosing in this open‐label trial was associated with a favourable tolerability and safety profile; the nature of the TEAEs was consistent with that observed in previous pivotal trials. Treatment with lacosamide was also associated with effective seizure control.     

A Clinical Study of the Skin Changes in Pregnancy in Kashmir Valley of North India: A Hospital Based Study

Background:

Pregnancy is associated with multiple skin changes, most of which are physiological in nature, being the direct result of expected modifications of the hormonal, vascular, metabolic or immunologic status in pregnant females. Pregnancy however is also associated with certain pruritic eruptions, which not only cause distress to the pregnant female, but may influence the fetal outcome as well.

Objective:

The objective of this study was to determine the pattern of skin changes associated with pregnancy and to identify the various clinical types of pregnancy specific dermatoses (PSDs).

Materials and Methods:

The study was a cross sectional study carried out at the out-patient Department of Gynecology and obstetrics of our hospital. A total of 650 pregnant females, irrespective of their parity and gestational age were screened for the presence of any dermatological complaint.

Results:

The age of the study population ranged from 17 to 39 years (mean age: 24 years). The study population included 272 (42%) primigravidae and 378 (58%) multigravidae. Physiological skin changes of pregnancy were seen in all patients, out of which linea nigra was the most common change, seen in 520 (80%) cases. Specific dermatoses of pregnancy were seen in 32 (4.9%) cases, which included (in the decreasing order of frequency) prurigo of pregnancy (50% cases), intrahepatic cholestasis of pregnancy (25% cases), polymorphic eruption of pregnancy (22% cases) and pemphigus gestationis (3% cases).

Conclusion:

Skin changes were seen in 100% of pregnant females in this study, the major proportion being formed by physiological skin changes of pregnancy though PSDs were also seen in a significant number.     

Thoracic surgery in Egypt

General thoracic surgery operations in Egypt are performed mainly by cardiothoracic surgeons and less oftenly by dedicated thoracic surgeons and general surgeons. This is mainly due to the relatively small number of thoracic surgeons in relation to population as only 210 cardiothoracic surgery specialists and 458 consultants are registered with the Egyptian Medical Syndicate (EMS) in a country with a population of more than 100 million people. Thoracic surgeons in Egypt are faced with a number of burdens, including the need to propagate the service to advanced technology infront of the obstacle of limited resources. Other burdens include higher incidence of TB, trauma and foreign body inhalation related to cultural backgrounds. More centres now are major video-assisted thoracic surgery (VATS) providing centres and others are specialized in more complex surgeries like complicated airway procedures and radical surgery for mesothelioma. As part of the international community, the COVID-19 pandemic has put more burdens on the thoracic surgery service as most centres have reduced their elective surgery workload to less than half of usual. Interestingly, the pandemic has allowed a self-referral screening programme with widespread Computed Tomography (CT) chest being performed among the population allowing thoracic surgeons to operate more on early stage lung cancer. The academic challenges for thoracic surgeons are even more with need for developing national databases. Nevertheless, thoracic surgeons in Egypt are optimistic regarding the future. The rising interest among the younger population will push training programs to meet the interests of enthusiastic junior surgeons. While the ancient history of thoracic surgery in Egypt seems to be extraordinary, the future perspectives promise to be more rewarding.     

The sensitivity and specificity of COVID‐19 rapid anti‐gene test in comparison to RT‐PCR test as a gold standard test

BackgroundCoronavirus disease 2019 (COVID‐19) is a modern infectious disease, first identified in December 2019 in Wuhan, China. The etiology is via severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), in a pandemic manner. The study aimed to compare between RT‐PCR and rapid anti‐gene tests for COVID‐19 with regard to sensitivity and specificity.MethodsThis is a cohort hospital‐based study done during the period of July to September 2020. Both rapid anti‐gene test kit (SARS‐CoV‐2) and RT‐qPCR were used for the detection of COVID‐19 in suspected cases.ResultsA total of 148 cases were tested using both the RT‐qPCR and rapid test. Twenty‐nine (19.6%) of these cases had positive results for RT‐qPCR and 119 (80.4%) were negative, whereas 52 (35.1%) patients were positive to rapid anti‐gene test and 96 (64.9%) of them negative. The sensitivity of the rapid test was 37.9%, the specificity was 65.5% and the accuracy was 64.44%. Rapid IgG test was positive in 47 (31.8) of cases. Although, rapid IgM test was positive in 18 (12.2%). The rapid IgG test was more sensitive than rapid IgM (Sensitivity 34.48% vs. 3.45%), but it was less specific than rapid IgM test (Specificity 68.91% vs. 85.71%).ConclusionWe cannot consider rapid anti‐gene test alone as a diagnostic method for COVID‐19. We should also conduct RT‐PCR test and other investigations like imaging CT scan of chest to confirm the diagnosis. The rapid IgG test is more sensitive than rapid IgM, but it was less specific.