Molecular pathology of NEU1 gene in sialidosis

Lysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme.     

Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.     

Matrix Metalloproteinase and Cytokine Profiles in Monocytes over the Course of Stroke

Stroke is a common cause of death and disability in our society. Stroke is associated with changes in immune responses within the central nervous system as well as systemically. The cells contributing to such changes as well as the factors contributing to formation of the inflammatory infiltrate observed in stroke remain to be clarified. In this study, blood monocytes and corresponding mononuclear cells (MNC) were separated and examined in parallel within 4 days and 1–3 months after onset of ischemic stroke. Numbers of TNF--, IL-12-, IL-6-, and IL-10-secreting cells and of cells expressing mRNA for matrix metalloproteinase (MMP)-1, -2, -7, -9 and tissue inhibitor of MMP (TIMP)-1 were studied. The TNF--, IL-12-, and IL-6-secreting monocytes and MNC were elevated during the acute phase compared to healthy controls. Such differences were not observed when stroke patients were examined during convalescence. The IL-10-secreting monocytes did not change over the course of stroke. Levels of monocytes expressing MMP-1, MMP-7 and TIMP-1 mRNA were elevated in the acute phase of stroke patients compared to convalescence and healthy controls, as were levels of MMP-1, -2, -7, -9 and TIMP-1 mRNA expressing blood MNC. The MMP-2 and -9 activity as measured by zymography also was higher in MNC supernatants in the acute phase of stroke compared to convalescence. The high levels of proinflammatory cytokines and MMPs in blood monocytes and MNC further demonstrate the presence of systemic aberrations in the acute phase of stroke. Such changes may contribute to the influx of blood-borne cells into the ischemic lesions during the acute phase of stroke.     

Persistent extramural vascular invasion positivity on magnetic resonance imaging after neoadjuvant chemoradiotherapy predicts poor outcome in rectal cancer

BackgroundIn rectal cancer, extramural vascular invasion (EMVI) is the presence of tumour cells in blood vessels outside the muscular layer, which is associated with poor prognosis. Regression of EMVI on MRI following neoadjuvant chemoradiotherapy or its persistence may have prognostic implications.MethodsThis retrospective study included 52 patients with rectal cancer who underwent total mesorectal excision following long-course neoadjuvant chemoradiotherapy (CRT). EMVI assessments were done on previous pelvic MRIs obtained before neoadjuvant CRT and eight weeks after the completion of neoadjuvant chemoradiotherapy in initially EMVI positive cases.ResultsPersistently EMVI positive patients had worse overall survival and disease-free survival compared to initially EMVI negative patients and patients who returned to negative (p < 0.001 for both). Multivariate analysis identified persistent EMVI positivity after neoadjuvant treatment (HR, 102.9; p = 0.003) as significant independent predictor of worse overall survival; and persistent EMVI positivity (HR, 17.0; p = 0.002), mesorectal fascia involvement after neoadjuvant treatment (HR, 8.0; p = 0.017), and poor differentiation (HR, 10.3, p = 0.012) as significant independent predictors of worse disease-free survival.ConclusionPersistent EMVI positivity after neoadjuvant therapy appears to be an independent factor for poor overall survival; and persistent EMVI positivity as well as mesorectal fascia involvement on post neoadjuvant therapy MRI and poor differentiation appears to be important predictors of poor disease-free survival in rectal cancer patients.     

Ultrasonography and erythrocyte distribution width in patients with plantar fasciitis

BackgroundThe measurement of plantar fascia thickness with ultrasonography can be used for both for diagnosis and as a response-to-treatment parameter in plantar fasciitis. Furthermore, with the recent studies, red cell distribution width may be used as an inflammatory marker. Aim of this study is to investigate the association of red cell distribution width and ultrasonography on diagnosis and monitoring of treatment in patients with plantar fasciitis.MethodsClinically diagnosed 102 patients with plantar fasciitis between the dates January 2016 to July 2018 were analysed. Hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plantar fascial ultrasonography were obtained on initial evaluation and in 1 month, 2 months and 3 months of the standard nonoperative treatment; American Orthopaedic Foot & Ankle Hindfoot Score (AOFAS) and Visual Analog Scale (VAS) scores were recorded. Posthoc and multivariate logistic regression analysis were used for statistical analysis on SPSS 21.0.ResultsRed cell distribution width was correlated with plantar fascia thickness by the end of the 1 month (r = 0.26, P = .013). Female sex, BMI over 30 kg/m², higher red cell distribution width and higher plantar fascia thickness were associated with plantar fasciitis on initial evaluation. Higher red cell distribution width together with higher plantar fascia thickness were also found to be a risk factor for both on initial evaluation and 1 month after treatment in plantar fasciitis.ConclusionThis study shows that association of red cell distribution width and plantar fascia thickness can be not only a diagnostic predictor but also an indicator of treatment response in plantar fasciitis.Level of clinical evidenceLevel IV     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Clostridium difficile acquisition rate and its role in nosocomial diarrhoea at a university hospital in Turkey

Infection with Clostridium difficile can present with various clinical pictures ranging from an asymptomatic carrier state to pseudomembranous colitis and plays an important part in the etiology of nosocomial diarrhoea. To identify risk factors for C. difficile colonization and diarrhoea in hospitalized subjects, patients admitted to a general medicine ward at Marmara University hospital during a one year period were entered into the study. Of the 202 patients, nosocomial diarrhoea developed in 45 (22.3%). Fourteen patients (6.9%) were colonized with C. difficile during their hospitalization period. Ten of the colonized patients (71.4%) developed diarrhoea and were found to be positive by toxin assay. Pseudomembranous colitis was confirmed endoscopically in 3 of the patients with diarrhoea. Administration of beta lactam agents such as ampicillin and cephalosporins; gastrointestinal manipulations and admission to the intensive care unit were found as major risk factors for C. difficile colonization.     

Augmentation of Shoulder Contour Using a Calf Implant

Sprengel deformity is a rare orthopedic condition that is associated with functional and cosmetic impairment. Results of orthopedic procedures are usually inconsistent and cosmetic results are far from satisfactory in these patients. A silicone-gel-filled calf prosthesis was used to correct the shoulder contour in a patient with Sprengel deformity. Cosmetically the deformity can be restored by using a calf implant for patients in whom orthopedic procedures are not likely to yield a satisfactory outcome.     

Immediate Continence Rates in RALRP: A Comparison of Three Techniques

Methods:We retrospectively analyzed the patients who underwent RALRP for localized prostate cancer by a single surgeon in our clinic from January 1, 2009–February 1, 2016. Continence was defined as no leakage or use of a safety pad for minimal leakage. The main outcome measure was continence at postoperative week 1 and months 1, 6, and 12.Results:Between 2009 and 2016, 239 patients underwent RALRP for localized prostate disease. Seventy-four patients underwent a standard approach (group 1), 88 had posterior reconstruction (group 2), and 77 had posterior reconstruction with total anatomic restoration (group 3). After 1 week, 24.3% of the patients in group 1 (18/74), 31.8% in group 2 (28/88), and 45.8% in group 3 (33/72) were continent (P = .02). One month after the surgery, continence rates for groups 1, 2, and 3 were 56.7, 67, and 75%, respectively (0.065). After 6 and 12 months, continence rates for groups 1, 2, and 3 were 72.9 and 87.8%, 81.8 and 89.7%, and 84.7 and 91.6%, respectively (P = .178 and .7484).Conclusion:Anatomic restoration improves continence rates in the early period after RALRP. Even though other parameters were higher in the total restoration group, immediate continence (at 1 week) was significantly better.