From recipe to research: introducing undergraduate students to the nature of science using a hybrid practical course centred on drug discovery for neglected diseases

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Powdered infant formula as a source of Salmonella infection in infants.

Powdered infant formula is not sterile and may be intrinsically contaminated with pathogens, such as Salmonella enterica, that can cause serious illness in infants. In recent years, at least 6 outbreaks of Salmonella infection in infants that have been linked to the consumption of powdered infant formula have been reported. Many of these outbreaks were identified because the Salmonella strains were unique in some way (e.g., a rare serotype) and a well-established Salmonella surveillance network, supported by laboratories capable of serotyping isolates, was in place. Another common feature of the outbreaks was the low level of salmonellae detected in the implicated formula (salmonellae may be missed in routine testing). These outbreaks likely represent only a small proportion of the actual number of Salmonella infections in infants that have been linked to powdered infant formula. Managing this problem requires a multidimensional approach in which manufacturers, regulators, and caregivers to infants can all play a role.     

Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology,radiology, and clinical evolution of disease

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon disorder of adult smokers associated with a significant morbidity. Arising from the aberrant accumulation of Langerhans and other immune cells, PLCH tends to cause a relatively isolated pulmonary involvement as compared to other forms of Langerhans cell (LC) and histiocytic disorders. Increased knowledge of cytokine triggers, dendritic cell trafficking, and clonality of LC populations in PLCH have resulted in an improved understanding of the pathobiology of PLCH. High-resolution CT (HRCT) of the chest has led to better appreciation of nodular and cystic radiographic abnormalities characteristic of the disease. Correlation of HRCT abnormalities with lung pathologic changes has led to an improved comprehension of clinical evolution of PLCH. Current clinical predictors for PLCH outcomes remain poor, although long-term follow-up and radiologic monitoring may help to define disease progression. This review discusses advances in PLCH emphasizing the etiopathologic bases of the disease and currently available radiologic modalities for monitoring disease progression.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Influence of Delays on Perforation Risk in Adults with Acute Appendicitis

Purpose  This study analyzed whether prehospital or in-hospital delay was the more significant influence on perforation rates for acute appendicitis and whether any clinical feature designated patients requiring higher surgical priority. Methods  A retrospective analysis was conducted over one year at a tertiary referral hospital without a dedicated emergency surgical theater. Admission notes, theater logbook, and the Hospital Inpatient Enquiry system were reviewed to identify the characteristics and clinical course of patients aged greater than 16 years who were operated upon for histologically confirmed acute appendicitis. Results  One hundred and fifteen patients were studied. The overall perforation rate was 17 percent. The mean duration of symptoms prior to hospital presentation was 38.1 hours with the mean in-hospital waiting time prior to operation being 23.4 hours. Although body temperature on presentation was significantly greater in patients found to have perforated appendicitis (P < 0.05), only patient heart rate at presentation and overall duration of symptoms, but not in-hospital waiting time, independently predicted perforation by stepwise linear regression modeling. Conclusion  In-hospital delay was not an independent predictor of perforation in adults with acute appendicitis although delays may contribute if patients are left to wait unduly. Tachycardia at presentation may be a quantifiable feature of those more likely to have perforation and who should be given higher surgical priority.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Psychotic Experiences Induced in Deluded Patients Using Distorted Auditory Feedback

The effect of hearing immediate auditory feedback of their own voice distorted in pitch was examined in 21 patients with a diagnosis of schizophrenia. Patients frequently reported that they heard a voice "speaking when I speak" and often attributed this "other" voice to an external agent: "I think it's an evil spirit speaking when I speak." The frequency of making these ''other''attributions was significantly related to degree of pitch distortion (rho = 0.62, P <.01) and to current severity of delusions (rho = 0.62, P <.01). However, the relationship with hallucinations was not significant (rho = 0.40) and there was no relationship with negative features such as psychomotor retardation. We conclude that the "hallucination-like" reports elicited by our paradigm resulted from an interaction between an unusual perceptual experience (distorted auditory feedback) and an abnormal mechanism for belief formation present in deluded patients. This formulation suggests a close relationship between delusions and hallucinations.     

Incidence of Low Back Pain After Lumbar Discectomy for Herniated Disc and Its Effect on Patient-reported Outcomes

Background

Long-term postdiscectomy degenerative disc disease and low back pain is a well-recognized disorder; however, its patient-centered characterization and quantification are lacking.

Questions/purposes

We performed a systematic literature review and prospective longitudinal study to determine the frequency of recurrent back pain after discectomy and quantify its effect on patient-reported outcomes (PROs).

Methods

A MEDLINE search was performed to identify studies reporting on the frequency of recurrent back pain, same-level recurrent disc herniation, and reoperation after primary lumbar discectomy. After excluding studies that did not report the percentage of patients with persistent back or leg pain more than 6 months after discectomy or did not report the rate of same level recurrent herniation, 90 studies, which in aggregate had evaluated 21,180 patients, were included in the systematic review portion of this study. For the longitudinal study, all patients undergoing primary lumbar discectomy between October 2010 and March 2013 were enrolled into our prospective spine registry. One hundred fifteen patients were more than 12 months out from surgery, 103 (90%) of whom were available for 1-year outcomes assessment. PROs were prospectively assessed at baseline, 3 months, 1 year, and 2 years. The threshold of deterioration used to classify recurrent back pain was the minimum clinically important difference in back pain (Numeric Rating Scale Back Pain [NRS-BP]) or Disability (Oswestry Disability Index [ODI]), which were 2.5 of 10 points and 20 of 100 points, respectively.

Results Systematic Review

The proportion of patients reporting short-term (6–24 months) and long-term (> 24 months) recurrent back pain ranged from 3% to 34% and 5% to 36%, respectively. The 2-year incidence of recurrent disc herniation ranged from 0% to 23% and the frequency of reoperation ranged from 0% to 13%.

Prospective Study

At 1-year and 2-year followup, 22% and 26% patients reported worsening of low back pain (NRS: 5.3 ± 2.5 versus 2.7 ± 2.8, p < 0.001) or disability (ODI%: 32 ± 18 versus 21 ± 18, p < 0.001) compared with 3 months.

Conclusions

In a systematic literature review and prospective outcomes study, the frequency of same-level disc herniation requiring reoperation was 6%. Two-year recurrent low back pain may occur in 15% to 25% of patients depending on the level of recurrent pain considered clinically important, and this leads to worse PROs at 1 and 2 years postoperatively.     

A statistical analysis of murine stem cell suicide techniques

The clinical application of soft agar cloning techniques for granulocyte-macrophage stem cells (CFU-C) has resulted in a number of contradictory reports that may in part be due to an inadequate data base. Growth of murine CFU-C is more reproducible and less variable than that of human CFU-C. We utilized in vivo hydroxyurea suicide of murine marrow CFU-C to address the question of how many experiments are needed to detect a specific difference with a p of less than 0.05. In 66 experiments the mean marrow CFU-C hydroxyurea kill was 23.3%; 6-9 separate experiments were necessary to detaect differences of 25%-30%. In order to be sure that a 25%-30% difference is not present, 15-21 experiments were required. Using a Dec-20 computer, 1000 samples of sample size 3, 4, or 10 were drawn from the 66 experiments; it was found that with 3 experiments and a true value of 23%, the actually observed value was below 10%, 17% of the time, and was over 40% in 10% of the samplings. In a smaller number of experiments similar results were obtained analyzing 3HTdR suicide of pluripotent stem cells and CFU- C. These data could provide a base from which to judge the validity of studies utilizing the CFU-C technique.