Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice

Autoimmune diabetes is characterized by an early mononuclear infiltration of pancreatic islets and later selective autoimmune destruction of insulin-producing beta cells. Lymphocyte homing receptors have been considered candidate targets to prevent autoimmune diabetes. L-selectin (CD62L) is an adhesion molecule highly expressed in naive T and B cells. It has been reported that blocking L-selectin in vivo with a specific antibody (Mel-14) partially impairs insulitis and diabetes in autoimmune diabetes-prone non-obese diabetic (NOD) mice. In the present study we aimed to elucidate whether genetic blockade of leukocyte homing into peripheral lymph nodes would prevent the development of diabetes. We backcrossed L-selectin-deficient mice onto the NOD genetic background. Surprisingly NOD/L-selectin-deficient mice exhibited unaltered islet mononuclear infiltration, timing of diabetes onset and cumulative incidence of spontaneous diabetes when compared to L-selectin-sufficient animals. CD4, CD8 T cells and B cells were present in islet infiltrates from 9-week-old L-selectin-sufficient and -deficient littermates. Moreover, total splenocytes from wild-type, heterozygous or NOD/L-selectin-deficient donor mice showed similar capability to adoptively transfer diabetes into NOD/SCID recipients. On the other hand, homing of activated, cloned insulin-specific autoaggressive CD8 T cells (TGNFC8 clone) is not affected in NOD/L-selectin-deficient recipients. We conclude that L-selectin plays a small role in the homing of autoreactive lymphocytes to regional (pancreatic) lymph nodes in NOD mice.     

Morbidity and Mortality Associated with Typhoid Fever Among Hospitalized Patients in Hyderabad District,Pakistan, 2017-2018: Retrospective Record Review

BackgroundHyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited.ObjectiveTo address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan.MethodsWe reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths.ResultsA total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06).ConclusionsAs this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures.     

Drug-Resistant Tuberculosis in Pet Ring-Tailed Lemur,Madagascar

We diagnosed tuberculosis in an illegally wild-captured pet ring-tailed lemur manifesting lethargy, anorexia, and cervical lymphadenopathy. Whole-genome sequencing confirmed the Mycobacterium tuberculosis isolate belonged to lineage 3 and harbored streptomycin resistance. We recommend reverse zoonosis prevention and determination of whether lemurs are able to maintain M. tuberculosis infection.     

A Rare Pattern of Ligamentous Injury of the Ankle: A Case Report and Review of the Literature

Ankle sprains are the most frequent sport related injuries with involvement of the lateral collateral ligament complex occurring in 85% of cases. Isolated anterior talofibular ligament injury is by far the commonest followed by combined anterior talofibular and calcaneofibular ligament strain. The posterior talofibular ligament is the strongest component of the lateral collateral ligament complex and is injured in severe ankle injury along with the other lateral collateral ligaments. While isolated calcaneofibular ligament strain has been reported, calcaneofibular ligament and posterior talofibular ligament strains with an intact anterior talofibular ligament are rare and reported in cadaveric studies. We present a case of radiologically diagnosed calcaneofibular ligament and posterior talofibular ligament injury and will discuss the anatomy, stress radiography, and magnetic resonance image findings and the mechanism of this particular injury.     

Efficiency of Soil Amendments for Copper Removal and Brassica Juncea (L.) Growth in Wastewater Irrigated Agricultural Soil

Wastewater irrigation is becoming a massive challenge for sustainable agriculture. Particularly, copper (Cu) presence in wastewater poses a great threat to the food chain quality. Thus, scientists need to address this issue by using chemical and organic soil amendments to restore the soil ecosystem. Therefore, this study aims to examine the efficacy of sulphur, compost, acidified animal manure and sesame straw biochar for Cu immobilization, adsorption and Brassica growth in wastewater irrigated soil. The current findings presented that all the soil amendments prominently improved brassica yield and significantly minimized the Cu uptake by Brassica shoots and roots in sesame straw biochar (SB) (64.2% and 50.2%), compost (CP) (48% and 32.5%), acidified manure (AM) (37% and 23.2%) and Sulphur (SP) (16% and 3.1%) respectively relative to untreated soil. In addition, Cu bioavailability was reduced by 51%, 34%, 16.6%, and 7.4% when SB, CP, AM, and SP were incorporated in wastewater irrigated polluted soil. The Cu adsorption isotherm results also revealed that SB treated soil has great potential to increase Cu adsorption capacity by 223 mg g^??1 over control 89 mg g^??1. Among all the treatments, SB and CP were considered suitable candidates for the restoration of Cu polluted alkaline nature soil.

     

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan

BackgroudDue to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA).MethodsA total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant.ResultsOut of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m². We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed.ConclusionsTibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.     

Transcranial Doppler sonography in craniosynostosis

In the management of craniosynostosis, there is a need for quantitative assessment of treatment methods and outcome. Radiology and pressure studies are well documented, but so far little attention has been given to cerebral blood flow changes and their possible relevance. This paper reports our initial experience using transcranial Doppler sonography to calculate the cerebrovascular resistance and cerebral blood velocities in the major basal vessels before and after surgery for craniosynostosis. Ten patients were studied using the Scimed 2-MHz probe through the temporal and frontal windows of the skull. Measurements were taken under standard physiological conditions before, during and after surgery. Preliminary results suggest that this non-invasive technique may be helpful in predicting and assessing the outcome following surgery for craniosynostosis.     

Additive effect of indomethacin and methotrexate on suppression of growth in rats

The purpose of this study was to investigate the medium-term effects of methotrexate (MTX) and indomethacin on the growth of young rats. Four equal groups of Sprague-Dawley male rats (four animals in each group; mean+/-S.D. body weight, 183+/-13 g, in their rapid growth phase) were subjected to the following drug treatment: one group was given MTX (0.2 mg kg(-1) body weight) subcutaneously on every fourth day, another received indomethacin (2.5 mg kg(-1) body weight) subcutaneously daily and the third group was given both of these drugs (MTX on every fourth day and indomethacin daily). The fourth group was injected subcutaneously with physiological saline every day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 10 weeks. After this period, liver, spleen and kidneys were excised, weighed and analysed for MTX and dihydrofolate reductase activity. Compared with the groups, which received MTX alone, indomethacin alone, or physiological saline, mean increase (17+/-11 g) in body weight of rats was minimal in the group receiving both MTX and indomethacin. The difference was statistically significant (p=0.001) when the values of mean increase in body weight of rats in different treatment groups after a 10-week treatment were compared. The mean weights of liver and spleen in this group receiving both MTX and indomethacin were also found to be significantly less than the weights of these organs in the control group (p<0.01). There also appears to be a decline in food consumption in this group (p<0.05). This negative effect on growth of animals in this group appears to be not only due to decreased food consumption but also due to increased inhibition of de novo pathway of DNA synthesis. This is supported by increased accumulation of MTX and decreased dihydrofolate reductase activity in this group receiving both MTX and indomethacin, as compared with the group receiving MTX alone. The data indicate an additive effect of MTX and indomethacin on the suppression of growth in young rats, alluding to the notion that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving these two drugs concomitantly over a long period of time might be at a risk of experiencing short-term suppression of growth.