Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo confocal microscopic characteristics of crystalline keratopathy in patients with monoclonal gammopathy: Report of two cases

In this paper, we report two cases of a 62-year-old patient presented with blurred vision and a 45-year-old male diagnosed with multiple myeloma who was referred from the Department of Oncology. Slit-lamp examination, in vivo confocal microscopy (IVCM), systemic work-up and serum protein electrophoresis were obtained. In both patients, slit-lamp findings revealed bilateral diffuse subepithelial and anterior stromal crystals and IVCM showed highly reflective deposits in the corneal epithelium and stroma. The first patient was eventually diagnosed with monoclonal gammopathy of undetermined significance following bone marrow biopsy and systemic evaluation. Unusual corneal deposits may constitute the first sign of monoclonal gammopathies. IVCM may be helpful in showing the crystalline nature of the corneal deposits and guiding the clinician to the diagnosis of gammopathies. Both ophthalmologists and oncologists should be aware that corneal deposits may herald a life-threatening hematologic disease.
Incentive spirometry combined with expiratory positive airway pressure improves asthma control and quality of life in asthma: a randomised controlled trial

Abstract Objectives: The use of the incentive spirometer (IS) and expiratory positive airway pressure (EPAP) provides several benefits in patients with respiratory disorders. However, the effects of the use of these devices coupled (IS + EPAP) are still unknown in asthmatic patients. The aim of this study was to evaluate the effect of IS associated with EPAP on exercise tolerance (six-minute walk test – 6MWT), lung function (by spirometry), asthma control (Asthma Control Questionnaire – ACQ) and quality of life (Asthma Quality of Life Questionnaire – AQLQ) in patients with severe asthma. Methods: Patients were randomised into two groups: IS + EPAP (n = 8) and control (n = 6). The IS + EPAP group performed breathing exercises at home, twice daily for 20 min, over a period of 5 weeks. Results: There was no significant difference in spirometric variables and in the distance walked in the 6MWT in both groups. However, the IS + EPAP group showed an improvement in asthma control (p = 0.002) and quality of life (p = 0.02). Conclusions: These findings demonstrate that the IS + EPAP protocol, when performed at home, provides an improvement in asthma control and quality of life for patients with severe asthma when evaluated by ACQ and AQLQ, respectively.
CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation

Abstract Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (Kiapp=8.6 μm). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time.
Reducing the average number of patients needed in a phase II trial through novel design

Abstract Phase II represents a very important part of the drug development process. It is important that genuinely effective treatments have a high chance of succeeding whilst treatments that will fail at phase III are screened out. Because of the high number of treatments available for testing and limited resources and patients available, it is increasingly of interest to apply novel designs to improve the efficiency of phase II trials. This paper shall argue that phase II presents the most promising area for applying novel designs and will review some recent developments in three classes of novel design: group-sequential designs, multi-arm designs, and enrichment designs. All three types of design considerably improve the efficiency of phase II trials on average and also ensure that patients are more likely to be treated with the best available treatment for them. Although the designs have drawbacks, the considerable advantages mean that these designs will become increasingly important in phase II.
Anxiety sensitivity as a mediator of the association between asthma and smoking

Abstract Objective: Despite its negative effects, smoking is more common among individuals with asthma compared to those without. Anxiety sensitivity (fear of arousal-related sensations) is associated with both smoking and asthma; however, no research, to date, has examined the interplay between these three factors. Thus, the purpose of the current study was to evaluate the mediating role of anxiety sensitivity in the association between asthma diagnosis and smoking status. Methods: The current study was a secondary analysis of data from three existing datasets of non-smokers and smokers with and without asthma (n = 433; 56.3% female, Mage = 34.01 years, SD = 13.9). Participants provided information on their asthma diagnosis status and smoking status and completed self-report measures. Results: As hypothesized, after controlling for gender, race and age, there was a significant indirect effect of asthma diagnosis on smoking status through anxiety sensitivity (95% CI = 0.07–0.48). Conclusions: These results indicate that the association between asthma diagnosis and smoking status appears to be driven, in part, by anxiety sensitivity and suggest that anxiety sensitivity may serve as an important target for prevention and intervention efforts for smokers with asthma.
Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Abstract Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.
A case of testicular germ cell carcinoma identified five years after lung metastasis resection

A 33 year-old man was referred to our center with swelling of the left scrotum. He underwent resection of the left testis,and pathological diagnosis indicated a germ cell tumor of that testis. His past history included lung cancer resection 5 yearsbefore the testicular surgery. Precise pathological reevaluation of the lung cancer using immunohistochemical methodsindicated that the tumor originally diagnosed as lung cancer was a metastasis of the germ cell tumor of the left testis.
The Chennai glaucoma study: Prevalence and risk factors for glaucoma in cataract operated eyes in urban Chennai

We report the prevalence and risk factors for glaucoma among aphakes and pseudophakes in 3850 subjects who participated in a population-based study in urban south India. The subjects underwent an ophthalmic examination including applanation tonometry, gonioscopy, optic disc evaluation and frequency doubling perimetry. Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria. Thirty eight, 15 aphakes and 23 pseudophakes (0.99% of 3850 subjects) of the 406 persons who had undergone cataract surgery were diagnosed with glaucoma. Aphakes/pseudophakes were at higher risk of glaucoma as compared to the phakic population (Odds Ratio: 2.71, 95% CI: 1. 94, 3.38, p=0.001). On multivariate analysis, older age and higher intra ocular pressure were risk factors for glaucoma. Blindness attributable to glaucoma was detected in 20% of aphakic and 4.3% of pseudophakic eyes. Glaucoma was a significant cause of morbidity in those who had undergone cataract surgery in this urban population.
Boston ocular surface prosthesis: An Indian experience

Context: Boston ocular surface prosthesis (BOSP) is a scleral contact lens used in the management of patients who are rigid gas permeable (RGP) failures as with corneal ectasias such as keratoconus and in those patients who have ocular surface disease such as Stevens–Johnson syndrome (SJS). Aim: To report utilization of BOSP in a tertiary eye care center in India. Materials and Methods: We retrospectively reviewed charts of 32 patients who received BOSP from July 2008 to May 2009. Indications for fitting these lenses, improvement in visual acuity (VA) before and after lens fitting and relief of symptoms of pain and photophobia were noted. Paired t-test was used for statistical analysis using SPSS version 16.0 for Windows. Results: Thirty-two patients (43 eyes) received these lenses. These consisted of 23 eyes of 17 patients who failed RGP trials for irregular astigmatism and corneal ectasia such as keratoconus and post radial keratotomy and scar and 20 eyes of 15 patients with SJS. Mean age of RGP failures was 27.94 years. Pre- and post-BOSP wear mean LogMAR VA was 1.13 and 0.29, respectively, in RGP failures. The P value was statistically significant (P < 0.001). In patients with SJS, LogMAR VA was 0.84 ± 0.92 before and 0.56 ± 0.89 after lens wear. The P value was statistically significant (P < 0.001). VA improved by >2 lines in 7/20 eyes (35%) with SJS, with improvement in symptoms. Conclusion: BOSP improves VA in patients who have irregular astigmatism as in ectasias and RGP failures and improves vision and symptoms in patients with SJS.
Pseudoangiomatous squamous cell carcinoma: a challenge for pathologists and plastic surgeons

Pseudo-angiosarcomatous or pseudovascular squamous cell carcinoma (SCC) of the skin is an unusual variant form of acantholytic SCC that mimics the histopathological appearance of angiosarcoma. We describe a case of pseudovascular SCC in a 77-year-old lady to highlight the frequent recurrence and aggressiveness, as well as the clinicopathological features of this rare form of cutaneous SCC, and demonstrate the difficulties in establishing the correct diagnosis. Plastic surgeons involved in the care of patients with cutaneous malignancies should be aware of this variant of SCC and its aggressive nature in order to manage these patients appropriately.
Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome

Abstract The CARMA1-BCL10-MALT1 (CBM) signalosome triggers canonical NF-κB signaling and lymphocyte activation upon antigen-receptor stimulation. Genetic studies in mice and the analysis of human immune pathologies unveiled a critical role of the CBM complex in adaptive immune responses. Great progress has been made in elucidating the fundamental mechanisms that dictate CBM assembly and disassembly. By bridging proximal antigen-receptor signaling to downstream signaling pathways, the CBM complex exerts a crucial scaffolding function. Moreover, the MALT1 subunit confers a unique proteolytic activity that is key for lymphocyte activation. Deregulated ‘chronic’ CBM signaling drives constitutive NF-κB signaling and MALT1 activation, which contribute to the development of autoimmune and inflammatory diseases as well as lymphomagenesis. Thus, the processes that govern CBM activation and function are promising targets for the treatment of immune disorders. Here, we summarize the current knowledge on the functions and mechanisms of CBM signaling in lymphocytes and how CBM deregulations contribute to aberrant signaling in malignant lymphomas.
Nine years’ review on preseptal and orbital cellulitis and emergence of community–acquired methicillin-resistant Staphylococus aureus in a tertiary hospital in India

Context: Preseptal cellulitis is the commonest orbital disease which frequently needs to be differentiated from orbital cellulitis. Prompt diagnosis and treatment with appropriate antibiotics can prevent vision loss and life-threatening complications of orbital cellulitis. Aims: To describe the clinical profile of cases with preseptal and orbital cellulitis admitted to a tertiary care hospital during a period of nine years. The causative organisms and the clinical outcome were analyzed. Settings and Design: Retrospective descriptive case study done in a tertiary care hospital in South India. Material and Methods: The in-patient records of patients with preseptal and orbital cellulitis were reviewed from 1998 to 2006. The factors reviewed included ocular findings aiding in the distinction of the two clinical conditions, the duration of symptoms, the duration of hospital stay, microbiological culture report of pus or wound swab, blood culture, drugs used for treatment, the response to therapy and complications. Statistical Analysis Used: Descriptive analysis. Results: One hundred and ten cases, 77 patients with preseptal cellulitis and 33 patients with orbital cellulitis were reviewed. Five percent of children and 21% of adults presented with cutaneous anthrax contributing to preseptal cellulitis. Thirty-nine percent cases with orbital cellulitis were caused by methicillin-resistant Staphylococcus aureus (MRSA). Conclusions: This study has helped in identifying organisms which cause orbital infections, especially community-acquired MRSA. It indicates the need for modifying our empirical antimicrobial therapy, especially in orbital cellulitis.
Assessing Framingham cardiovascular risk scores in subjects with diabetes and their correlation with diabetic retinopathy

Aim: To study the Framingham cardiovascular risk assessment scores in subjects with diabetes and their association with diabetic retinopathy in subjects with diabetes. Materials and Methods: In this population-based prospective study, subjects with diabetes were recruited (n=1248; age ≥40 years). The Framingham cardiovascular risk scores were calculated for 1248 subjects with type 2 diabetes. The scores were classified as high risk (>10%), and low risk (<10%). Results: Out of the 1248 subjects, 830 (66.5%) patients had a low risk of developing cardiovascular disease (CVD) in 10 years and 418 (33.5%) had a high risk of developing CVD in 10 years. The risk of developing CVD was more in males than females (56.8% vs. 7%) The prevalence of both diabetic retinopathy and sight-threatening retinopathy was more in the high-risk group (21% and 4.5%, respectively). The risk factors for developing diabetic retinopathy were similar in both the groups (low vs. high) – duration of diabetes (OR 1.14 vs. 1.08), higher HbA1c (OR 1.24 vs. 1.22), presence of macro- and microalbuminuria (OR 10.17 vs. 6.12 for macro-albuminuria) and use of insulin (OR 2.06 vs. 4.38). The additional risk factors in the high-risk group were presence of anemia (OR 2.65) and higher serum high density lipoprotein (HDL) cholesterol (OR 1.05). Conclusion: Framingham risk scoring, a global risk assessment tool to predict the 10-year risk of developing CVD, can also predict the occurrence and type of diabetic retinopathy. Those patients with high CVD scores should be followed up more frequently and treated adequately. This also warrants good interaction between the treating physician/cardiologist and the ophthalmologist.
Safety and Efficacy of Antimicrobial Mouthrinses in Clinical Practice

Efficacy Overview. The use of an antimicrobial mouthrinse is an important adjunct to toothbrushing and interdental cleaning. To varying degrees, chlorhexidine gluconate (CHG), cetylpyridinium chloride (CPC), and essential oils (EO) interrupt the integrity of the bacterial cell membrane, leading to lysis and death. CHG binds to salivary mucins, tooth structure, dental plaque, and oral soft tissues and is released slowly into the mouth, where it inhibits adsorption of bacteria onto teeth. CHG is active against a wide range of gram-positive and gram-negative microorganisms. CPC binds to teeth and plaque to a lesser degree than CHG and is generally less efficacious than CHG. CHG and EO penetrate plaque biofilm and produce changes in microbial cell surface morphology that alter coaggregation, recolonization, and, thus, survival. CHG, CPC, and EO are active against a wide variety of aerobic and anaerobic bacteria. An overview of the Food and Drug Administration and American Dental Association rigorous approval processes for efficacy and safety is provided. Safety Overview. Long-term use of CHG or EO does not adversely affect the ecology of oral microbial flora, including microbial overgrowth, opportunistic infection, or development of microbial resistance. Long-term use of CHG, CPC, or EO does not contribute to soft tissue lesions or mucosal aberrations and has no serious adverse effect on salivary flow, taste, tooth deposits, or dental restoration. There is no evidence of a causal link between alcohol-containing mouthrinses and the risk of oral and pharyngeal cancer.
Strategies in relative and absolute quantitative mass spectrometry based proteomics

Abstract Quantitative mass spectrometry approaches are used for absolute and relative quantification in global proteome studies. To date, relative and absolute quantification techniques are available that differ in quantification accuracy, proteome coverage, complexity and robustness. This review focuses on most common relative or absolute quantification strategies exemplified by three experimental studies. A label-free relative quantification approach was performed for the investigation of the membrane proteome of sensory cilia to the depth of olfactory receptors in Mus musculus. A SILAC-based relative quantification approach was successfully applied for the identification of core components and transient interactors of the peroxisomal importomer in Saccharomyces cerevisiae. Furthermore, AQUA using stable isotopes was exemplified to unraveling the prenylome influenced by novel prenyltransferase inhibitors. Characteristic enrichment and fragmentation strategies for a robust quantification of the prenylome are also summarized.
Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor and stroma cells. In this patient cohort, elevated stroma cell KLK4 expression, but not tumor cell KLK4 expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis (hazard ratio: 2.12, p<0.01). Likewise, univariate analysis revealed a trend for statistical significance of elevated KLK4 stroma cell expression for overall survival of TNBC patients as well.
Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease

Objective. —To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers. Design. —Multicenter, prospective study of infants born to HIV-seropositive mothers. Setting. —A total of 62 obstetric and pediatric centers in France. Participants. —Of 1386 children born to HIV-1—seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before this age. Main Outcome Measure. —Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth. Results. —The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0;P Conclusions. —These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention. (JAMA. 1996;275:606-610)
Maintaining protein composition in cilia

Abstract The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.