Slime Production by Staphylococcus aureus and Staphylococcus epidermidis Strains Isolated from Patients with Diabetic Foot Ulcers

Slime production is a very important factor related to biofilm formation. The objective of the present study was to determine the frequency of slime production by Staphylococcus aureus and Staphylococcus epidermidis strains recovered from 50 patients with diabetic foot ulcers. Slime production was determined using the Congo red agar (CRA) method and compared with immunocytochemistry for the production of polysaccharide intercellular adhesin (PIA). Out of 55 S. aureus strains, 69% produced slime as shown by the CRA method. Of them, 84.2% also produced PIA. Of 17 CRA-negative strains, 70.6% produced PIA. Out of 20 S. epidermidis strains, 75% were CRA positive and 93.3% produced PIA. All CRA-negative S. epidermidis produced PIA. In conclusion, PIA production is a very common trait of S. aureus and S. epidermidis isolates obtained from diabetic foot ulcer patients.     

Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic targets in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) has a relatively high mortality rate and poor prognosis. Recently, we showed that overexpression of phosphorylated (p) nuclear factor-kappaB (NF-kappaB) in squamous cell carcinoma of the tonsil (SCCT) and high grade dysplasia is associated with a poor prognosis. Because the mammalian target of the rapamycin (mTOR) pathway contributes to the activation of NF-kappaB through immunophilin/mTOR signaling, we investigated: (a) the immunohistochemical expression and state of activation and potential clinical significance of components of the mTOR signal transduction pathway in SCCT patients (morphoproteomics); and (b) the inhibitory effects of rapamycin on the growth and state of activation of mTOR in 2 HNSCC cell lines (pharmacoproteomics). Archival biopsy materials from 39 patients with SCCT were studied by immunohistochemistry for the expression of p-mTOR (Ser 2448), and p-p70S6K (Thr 389), and/or cyclin D1. Results for SCCT were compared with adjacent non-neoplastic epithelium, when present, and with normal tonsillar epithelium from approximately age-matched controls; clinical outcomes were also assessed. SCCT showed mTOR (Ser 2448) expression in 93% (30/32 cases) with 2+ or 3+ plasmalemmal and/or cytoplasmic intensity in 84% vs 42% in surface epithelium from normal tonsils (p <0.001). The mean combined expression score (signal intensity x percentage of positive cells) for p-p70S6K was significantly greater in the SCCT group vs adjacent non-neoplastic squamous epithelium and normal tonsillar epithelium of the control group (p <0.05). A relationship existed between higher p-p70S6K expression levels in the non-neoplastic squamous epithelium adjacent to the SCCT and increased risk of death from disease (hazard ratio = 7.9; 95% confidence interval (CI) = 2.1 to 29.9; p = 0.002). There was also a relationship between nuclear expression of cyclin D1 in SCCT and shortened recurrence-free survival (p = 0.015). Two human HNSCC cell lines, SCC-15 and FaDu, were incubated with and without rapamycin to assess its impact on growth and on the expression of p-mTOR. Rapamycin in a dose-dependent fashion inhibited growth more in SCC-15, which correlated with a greater reduction in constitutively activated p-mTOR (Ser 2448) as shown by Western blotting. In conclusion, these morphoproteomic and pharmacoproteomic data collectively provide a rationale for selecting mTOR effectors as therapeutic targets in HNSCC.     

Deep brain stimulation and motor cortex and spinal cord stimulation in the treatment of movement disorders and pain syndromes -- the theoretical baseline and practical guidelines

The authors present the current views on the use of electrical stimulation in selected movement disorders (Parkinson's disease, dystonia) and pain syndromes (central and neuropathic pain) refractory to pharmacological therapy. Stimulation should be applied in cases with an established diagnosis (especially Parkinson's disease and dystonia) and with a lack of efficacy despite the best available medical therapy. Therefore it should be the last treatment option, except of generalized dystonia, where it seems to be nowadays the treatment of choice. Suggested selection criteria are based on experience of different centers and on current medical literature. They are published to make the procedure more rational and more available in Poland.     

Ammonia at pathophysiologically relevant concentrations activates kynurenic acid synthesis in cultured astrocytes and neurons

The synthesis of the NMDA receptor glycine site antagonist kynurenic acid (KYNA) from exogenously added kynurenine was measured in cultured cerebral cortical neurons, cortical astrocytes and an oligodendroglial cell line OLN-93, incubated for 2 h in the presence or absence of ammonium acetate ("ammonia") at 0.1-10 mM concentration. In neurons ammonia stimulated KYNA synthesis to approximately 160-170% of control at 0.1-1.0mM, did not produce any effect at 2.5 and 5 mM, and inhibited the synthesis to approximately 80% of control at 10mM concentration. In astrocytes, a stimulation to approximately 200% of control occurred in the whole ammonia concentration range. No effect of ammonia was noted in OLN-93 cells. Increased KYNA synthesis may represent a cytoprotective response of astrocytes and neurons against the NMDA receptor-mediated cytotoxic activity of ammonia.     

Heterogeneity in executive impairment in patients with very mild Alzheimer's disease

BACKGROUND/AIMS: The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD. METHODS: Thirty-six patients with very mild AD (MMSE scores above 23) and 32 healthy control subjects were administered a battery of 7 executive tests: Trail Making part B, Stroop Interference Test, modified Wisconsin Card Sorting Test (WCST), category- and letter-based verbal fluency, a design fluency task and the Similarities subtest from WAIS. Impairment was defined as a score of 2 SD or more below control means. RESULTS: Executive impairment on at least 1 measure was seen in 76% of the patients, and 50% were impaired on 2 or more tests. Trail Making B and Stroop Interference Test were impaired in more than 40%, whereas only few patients were impaired on Similarities, WCST and design fluency. A wide variation of executive test profiles was seen among the patients. CONCLUSION: Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients. Complex attentional skills are more frequently affected than other executive functions. There is, however, considerable heterogeneity among AD patients in the pattern of executive dysfunction.     

Serum sickness disease in a patient with alopecia areata and Meniere’ disease after PRP procedure

Background: Platelet rich plasma procedure (PRP) is considered to be one of the safest aesthetic procedures. Adverse reactions after PRP administration are extreme rare. Purpose: We present the patient with serum sickness disease (SSD) after PRP procedure. Objective and methods: 41 years old female suffers from alopecia areata for 5 years with frequent relapses and she has been suffering from Menier's disease recurrent symptoms for 6 years. The patient developed SSD after third PRP rejuvenating procedure and she has also noticed new alopecia areata lesions, but without Menier's disease symptoms. After SSD, 4 months later, she developed severe symptoms of Menier's disease with an episode of sudden sensorineural hearing loss. It alleviated only after intravenous administration of methylprednisolone. In our opinion, significant contraindication of PRP procedure is an autoimmune disease in the active phase.     

The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe): a protocol of a prospective,cohort study of causes of mortality among preterm births and stillbirths

Background

In South Asia, where most stillbirths and neonatal deaths occur, much remains unknown about the causes of these deaths. About one-third of neonatal deaths are attributed to prematurity, yet the specific conditions which cause these deaths are often unclear as is the etiology of stillbirths. In low-resource settings, most women are not routinely tested for infections and autopsy is rare.

Methods

This prospective, cohort study will be conducted in hospitals in Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth or a preterm birth at one of the hospitals will be eligible for enrollment. With consent, the participant and, when applicable, her offspring, will be followed to 28-days post-delivery. A series of research tests will be conducted to determine infection and presence of other conditions which may contribute to the death. In addition, all routine clinical investigations will be documented. For both stillbirths and preterm neonates who die ≤ 28 days, with consent, a standard autopsy as well as minimally invasive tissue sampling will be conducted. Finally, an expert panel will review all available data for stillbirths and neonatal deaths to determine the primary and contributing causes of death using pre-specified guidance.

Conclusion

This will be among the first studies to prospectively obtain detailed information on causes of stillbirth and preterm neonatal death in low-resource settings in Asia. Determining the primary causes of death will be important to inform strategies most likely to reduce the high mortality rates in South Asia.

Trial registration

Clinicaltrials.gov (NCT03438110) Clinical Trial Registry of India (CTRI/2018/03/012281).

     

Importance rating of risk factors of ischemic stroke in patients over 85 years old in the polish population

Introduction

The European population is aging and the number of elderly patients suffering from ischemic brain stroke increases. A better knowledge of the correlation between the risk factors and the course of the disease in old people may be useful for planning medical care and prophylactic strategies.

Effect of Kynurenic Acid on Pupae Viability of <Emphasis Type="Italic">Drosophila melanogaster cinnabar</Emphasis> and <Emphasis Type="Italic">cardinal</Emphasis> Eye Color Mutants with Altered Tryptophan-Kynurenine Metabolism

Kynurenic acid (KYNA) is one of the metabolites of evolutionary conserved tryptophan (Trp)/kynurenine (Kyn) metabolic pathway. Elevation of KYNA contributes to development of psychosis in schizophrenia but attenuates neurodegeneration in Drosophila model of Huntington’s disease. We have reported that KYNA increased lethality of pupae of wild-type flies, but not of vermilion (v) mutants with impaired formation of Kyn from Trp, suggesting that KYNA toxicity depends on its interaction with downstream Kyn metabolites [i.e., 3-hydroxykynurenine (3-HK) and/or xanthurenic acid (XA)]. The present study aimed to further explore the mechanisms of KYNA-induced lethality by the assessment of KYNA effect on pupae of two Drosophila mutants: cinnabar (cn), characterized by higher KYNA and lower 3-HK production, and cardinal (cd), characterized by higher 3-HK and XA levels compared to wild-type flies. Our microarray datamining revealed that the gene expression pattern of enzymes forming Trp/Kyn pathway stands in line with previously reported developmental changes in KYNA, 3-HK, and XA concentrations in wild-type and mutant flies. Administration of KYNA increased pupae lethality in cd, but not in cn mutants. Present data suggest that toxic effect of exogenous KYNA depends on the presence of 3-HK and/or XA. This is further supported by our finding that early stages of Drosophila development are associated with a positive expression pattern of genes encoding sulfotransferases, enzymes that are inhibited by KYNA and are involved in detoxification of XA. Alternatively, the toxic effect of KYNA might depend on anti-proliferative effects of KYNA.