In vitro antifungal susceptibility of the dermatophytes: a single center study from Eastern Black Sea Region of Turkey.

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum (13.8% in 49 samples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development.

Analysis of treatment adherence in patients undergoing phototherapy.

OBJECTIVE: Phototherapy is a convenient and effective treatment alternative for a range of skin diseases. However, a major challenge in patient adherence to phototherapy may be the necessity of visiting a phototherapy center regularly over an extended period of time. The aims of this study were (i) to investigate the adherence rate to phototherapy and (ii) to determine factors associated with adherence to narrow-band ultraviolet B phototherapy (nbUVB) treatment. PATIENTS AND METHODS: A retrospective review of patient records who underwent nbUVB phototherapy between January 1, 2018, and March 31, 2023, was performed. Patient records were reviewed for age, gender, skin type, diagnosis, type of phototherapy applied, duration of treatment, total number of sessions, presence of side effects, reasons for discontinuation of treatment, and perceived benefits of treatment. RESULTS: Of a total of 729 patients undergoing phototherapy, 281 (38.5%) discontinued treatment before completing 20 sessions. In particular, younger patients and those who experienced fewer side effects tended to discontinue treatment prematurely. The most common reason for discontinuing treatment was difficulty in visiting the hospital regularly. CONCLUSIONS: The patient's compliance with phototherapy was 61.5%. These results indicate that phototherapy is still one of the preferred treatment methods, although many new treatment agents have been developed in dermatology in recent years. Identifying and addressing factors that affect patient adherence will certainly help increase the effectiveness of treatment.

White matter tracts that overlap with the thalamus and the putamen are protected against multiple sclerosis pathology.

BACKGROUND: The thalamus and the putamen are highly connected hubs implicated in multiple sclerosis (MS) pathology. It remains unclear if white matter (WM) tracts, which pass through them, have a different susceptibility to MS pathology, and if so, if their impact on disability predominates over that exerted by disease in other WM tracts. We hypothesized that WM tracts connected to and passing through these hubs (subsequently termed hub+ tracts) would be more susceptible to MS-related pathology than tracts that do not pass through them (hub- tracts) due to retrograde and anterograde distant degeneration. Thus, we compared the lesion load and neurite orientation dispersion and density imaging (NODDI) derived metrics between hub+ and hub- tracts and assessed the relationship between these MRI metrics and those of physical impairment. METHODS: Eighteen patients (mean age of 45.5 years, 12 females) had 3 Tesla MRI consisting of T1-weighted and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR), and NODDI from which the orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (IVF) were derived. Forty-nine WM tracts, i.e., 12 hub+ and 37 hub- tracts, were segmented out. Exploratory analyses of the differences in lesion burden, whole tract and normal appearing WM (NAWM) NODDI metrics were carried out between the two types of tracts using a Mann-Whitney U test. Correlations with physical impairment, quantified using the expanded disability status scale (EDSS) and timed 25-foot walk (T25FW) test were assessed using Spearman correlation analyses. RESULTS: Hub- tracts had larger T1- (p<0.001) and T2-lesion (p<0.001) volumes; lower ODI (p<0.001), NDI (p<0.001) and higher IVF (p = 0.020) in comparison to hub+ tracts. Measures of tissue injury in hub+ tracts correlated with those of clinical disability, though less strongly than in hub- tracts. CONCLUSIONS: Contrary to our hypothesis, our exploratory pilot study results suggest that WM tracts that overlap with the thalamus and the putamen have a lower degree of lesional and non-lesional tissue injury, suggesting a protective role of the hubs against MS pathology or a higher degree of vulnerability of those not passing through hub stations. We also show a weaker association between disability impairment and hub+ pathology, compared to that in hub- tracts. Our findings point to a potential role of disease location in relation to hubs as guidance for treatment personalization in MS.

Volume and Infusion Rate Dynamics of Intraparenchymal Central Nervous System Infusion in a Large Animal Model.

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. Translation of thalamic injection to patients carries risks in that (1) it has never been done in humans, and (2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 µL) and rates (0.5-5 µL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for ∼1 month postinjection with magnetic resonance imaging (MRI) performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 µL (2 × the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 and 26 h) could have contributed to the generation of larger lesions. The target volume (400 µL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 µL/min at a volume ∼1/3 of the thalamus (400-600 µL) appears to be well tolerated in sheep both clinically and histopathologically.

A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone. CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping.

Abnormal metabolism has been reported in bipolar disorder, however, these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.

Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma.

AIM OF THE STUDY: Important signalling pathways play fundamental roles in the pathogenesis of thyroid carcinoma (TC). PTEN, mTOR, PI3K-p85 and K-Ras are the principal factors involved in these signalling pathways. To immunohistochemically examine the expressions of PI3K, mTOR and PTEN in patients suffering from follicular TC, papillary TC or variants thereof, as well as to investigate KRAS mutations via PCR to determine their clinical and prognostic relevance to differentiated thyroid cancer. MATERIAL AND METHODS: The expression of PTEN, PI3K-p85 and mTOR was immunohistochemically examined, and the mutation of K-Ras was examined via PCR. The results obtained were compared to the clinico-pathologic characteristics of the patients. RESULTS: A significant correlation was found between p85 expression and lymphovascular invasions and between PTEN expression and multifocality (p = 0.048 and p = 0.04, respectively), and a correlation between p85 and capsular invasion was found, with a borderline statistical significance (p = 0.056). No expression of PTEN, p85 or Mtor was detected in normal tissue. K-Ras mutation was examined in 66 of the 101 patients (57.4%), and the percentage of patients exhibiting a K-Ras mutation was 17.4%. All of the patients exhibiting a K-Ras mutation were women (p = 0.047). The disease-free survival was 44.6 months (95% CI: 37.9-51.3) and was statistically significantly higher in the group that displayed level 1 or lower expression of p85 (p = 0.043). CONCLUSIONS: The expression levels of the aforementioned markers were significantly higher in TC cells than in normal tissue. A significant correlation was detected between K-Ras mutation and gender. This study demonstrates that p85 and PTEN are markers that should be evaluated in further studies of TC.

Demographical, laboratory and associated findings in patients with perniosis.

BACKGROUND: Perniosis is a cold-induced inflammatory disorder of the acral areas. The objective of this study was to investigate the demographic characteristics, associated factors, clinical and laboratory findings in patients with perniosis and to compare those findings between patients who had recurrent and acute disease. METHODS: Thirty-four patients with perniosis were investigated retrospectively for age, gender, occupation, smoking and diet histories, associated diseases, family history of perniosis, precipitating factors, the month of onset and the duration of perniosis, the distribution of the lesions and the results of laboratory investigations. RESULTS: Fifteen patients were male and 19 were female. The ages of the patients ranged from 15 to 57 years. Thirteen patients were working as sales people, which was the most common occupation. Sixteen patients were smokers. While 25 of the patients had encountered perniosis for the first time, in 9 of the patients, there were recurrent lesions. Diseases other than perniosis were recorded in 6 of the patients. The laboratory tests revealed mild leukopenia in 2, antinuclear antibody (ANA) positivity in 3, mild rise in albumin level in serum protein electrophoresis in 1 patient. ANA positivity was significantly higher in patients with recurrent disease. CONCLUSION: Perniosis was more common in women and below 40 years. We found no significant laboratory findings except ANA positivity in patients with recurrent perniosis.

Combined therapy of teicoplanin and caffeic acid phenethyl ester (CAPE) in the treatment of experimental mediastinitis in the rat.

Post-sternotomy mediastinitis affects 1-3% of patients undergoing cardiac surgery and is lethal in 10-47% of these patients. We investigated the effect of an antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE), in the attenuation of inflammatory response induced by methicillin-resistant Staphylococcus aureus (MRSA) infection in a rat experimental mediastinitis model. Rats, divided into six equal groups, received MRSA precolonized stainless steel wire pieces implanted into their mediastinal spaces. Control group and CAPE control group received saline and CAPE 10 micromol/kg.day(-1 )respectively, where Group A received a single dose of teicoplanin 24 mg/kg i.m. for the first day and then 12 mg/kg.day(-1) . Group B received teicoplanin as in Group A plus CAPE 10 micromol/kg. day(-1 )intra-peritoneally. Group C received teicoplanin 60 mg/kg i.m. for the first day and then 30 mg/kg.day(-1 )and Group D received teicoplanin as in Group C plus CAPE 10 micromol/kg.day(-1) . By the end of 14 days rats were sacrificed and serum malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), urea and creatinine levels were evaluated. Mediastinal organ tissues were collected for histopathological analysis. Infection rates in all the drug-treated groups were lower than the control groups ( P=0.002) but statistical significance was attained only between the groups A and D ( P=0.018). In connective tissues and the peribronchial area polymorphonuclear leukocytic (PNL) infiltration in the treatment groups, although becoming very close, did not reach statistical significance (P =0.053, P=0.075, respectively). PNL infiltration especially in the peribronchial tissues of the Group B animals was found to be significantly less than the Control and CAPE Control groups with P values of 0.013 and 0.010, respectively. MDA and MPO levels were significantly lower in the treatment groups ( P<0.001 and P<0.001 respectively). Levels of the degradation products of NO were lower in treatment groups compared to two control groups (P=0.003, P= 0.005). NO levels in Group D were lowest among all treatment groups ( P=0.001). It has been demonstrated that although bacterial colonization can be controlled in mediastinitis, the inflammatory response persists. The combination of an antioxidant / anti-inflammatory agent, CAPE, added to standard antibiotic therapy might be effective in the treatment of post-sternotomy mediastinitis due to MRSA.

Effects of heat stress on growth, some blood variables and lipid oxidation in broilers exposed to high temperature at an early age.

1. This study was conducted to determine metabolic and physiological responses of 2 commercial broiler strains, Hubbard (H) and Cobb (C), exposed to an ambient temperature of 38 degrees +/- 1 degree C for 2 h at 14 and 15 d of age. 2. Exposure to high temperature at an early age resulted in weight loss in strain C, which was not compensated for by 35 d of age but there was no weight loss in strain H. 3. Exposure of broilers to heat stress (38 degrees +/- 1 degree C) at 35 d of age resulted in an increase in rectal temperature, regardless of previously high temperature experience but acid-base balance and haematocrit values were not affected by heat stress. 4. Malondialdehyde concentration was higher in unexposed birds than in previously exposed ones and did not significantly differ between strains.

Body weights, carcase characteristics, organ weights, abdominal fat, and lipid content of liver and carcase in two lines of Japanese quail (Coturnix coturnix japonica), unselected and selected for four week body weight.

1. The present study was conducted on quails to evaluate the effects of line and sex on body weight, carcase characteristics and organ weights and also to evaluate the effect of line on sex organs, and on carcase and liver lipid content of male quails. 2. Chicks of both sexes were weighed weekly until 6 weeks when they were slaughtered. Carcase yield, parts yield and measurement, weight of liver, heart, gizzard, abdominal fat and sex organs were obtained. Carcase and liver lipid content of male quails were determined. 3. Weights of body, carcase, breast, thigh, liver, heart, gizzard, abdominal fat, tests and ovary, yield of testes were affected by line. Line had no significant effect on the yields of carcase, breast, thigh, liver, heart, gizzard plus heart plus liver, abdominal fat and ovary. Carcase and liver lipid contents of male quails were affected by line.

Influence of various dietary protein levels on carcase composition in the male Japanese quail (Coturnix coturnix japonica).

1. The present study was conducted to determine the effect of various dietary protein concentrations on the carcase composition of male Japanese quail. 2. Six diets varying in protein from 160 to 300 g/kg and containing approximately 11.72 MJ/kg ME were fed for 5 weeks and analysed for dry matter, protein, fat and ash. 3. Treatments affected carcase weight, dry matter, protein, ether extract and ash (P < 0.01). 4. The water content of the carcases decreased with increasing dietary protein concentrations, while the carcase protein content increased with higher dietary protein. The carcases with the highest fat content were obtained from quail receiving the low protein diet.