Subclinical hypothyroidism and conception in a woman with primary infertility

Hypothyroidism is the most common endocrinological problem affecting women who present with ovulatory dysfunction resulting in infertility.It’s milder form, subclinical hypothyroidism (SH) characterized by mildly elevated thyroid stimulating hormone levels and normal free thyroxine levels, may also contribute to disturbed reproductive function. We report a case highlighting the beneficial effects of levothyroxine replacement therapy in women with subclinical hypothyroidsm presenting with infertility

Fabrication and characterization of chitosan nanoparticles and collagen-loaded polyurethane nanocomposite membrane coated with heparin for atrial septal defect (ASD) closure

Atrial septal defect (ASD) constitutes 30–40% of all congenital heart diseases in adults. The most common complications in the treatment of ASD are embolization of the device and thrombosis formation. In this research, an occluding patch was developed for ASD treatment using a well-known textile technology called electrospinning. For the first time, a cardiovascular occluding patch was fabricated using medical grade polyurethane (PU) loaded with bioactive agents namely chitosan nanoparticles (Cn) and collagen (Co) which is then coated with heparin (Hp). Fourier transform infrared spectrum showed characteristic vibrations of several active constituents and changes in the absorbance due to the inclusion of active ingredients in the patch. The contact angle analysis demonstrated no significant decrease in contact angle compared to the control and the composite patches. The structure of the electrospun nanocomposite (PUCnCoHp) was examined through scanning electron microscopy. A decrease in nanofiber diameter between control PU and PUCnCoHp nanocomposite was observed. Water uptake was found to be decreased for the PUCnCoHp nanocomposite against the control. The hemocompatibility properties of the PUCnCoHp ASD occluding patch was inferred through in vitro hemocompatibility tests like activated partial thromboplastin time (APTT), prothrombin time (PT) and hemolysis assay. It was found that the PT and APTT time was significantly prolonged for the fabricated PUCnCoHp ASD occluding patch compared to the control. Likewise, the hemolysis percentage was also decreased for the PUCnCoHp ASD patch against the control. In conclusion, the developed PUCnCoHp patch demonstrates potential properties to be used for ASD occlusion

Tuberculosis of the sella masquerading as pituitary adenoma

Tuberculosis of the central nervous system is an ominous consequence of disseminated tuberculosis which usually manifests as meningitis, an abscess or rarely as a tuberculoma. Though infrequent, intracranial tuberculomas especially within the sella, are notorious for simulating as pituitary tumors, by jeopardising pituitary hormonal function and exerting compressive effects on adjacent intracranial structures. However, a prompt evaluation can help tackle this diagnostic challenge with timely institution of anti-tuberculosis treatment, (ATT). Although in rare instances surgery may be a favourable option especially for managing extensive intrasellar masses, ATT usually facilitates resolution of such lesions. Long term hormonal replacement therapy may be required for established endocrine dysfunction

Wpływ badań oceniających bezpieczeństwo sercowo-naczyniowe na wybór preparatu insuliny w leczeniu cukrzycy typu 2: opinia ekspertów

Wstęp: Niniejszą opinię ekspertów opracowano w celu omówienia epidemiologii i patofizjologii chorób układu sercowo-naczyniowego (CVD) u chorych na cukrzycę typu 2 (T2DM), wyjaśnienia różnych zagadnień statystycznych i niuansów w interpretacji wyników badań oceniających bezpieczeństwo sercowo-naczyniowe (CVOT) ze szczególnym zaakcentowaniem badań typu CVOT dotyczących insulinoterapii i ich wpływu badań na wybór preparatów insuliny w codziennej praktyce klinicznej. Metody: Grupa ekspertów krytycznie przeanalizowała opublikowane dane z badań obserwacyjnych, badań klinicznych z randomizacją, metaanaliz i badań CVOT dotyczących bezpieczeństwa stosowania preparatów insuliny w odniesieniu do układu sercowo-naczyniowego i uzgodniła serię opinii popartych dostępnymi dowodami naukowymi i oceną kliniczną ekspertów. Wyniki: Wielu chorych na T2DM charakteryzuje się wysokim ryzykiem CVD i zgonu sercowo-naczyniowego, które częściowo wynika z czynników ryzyka związanychz insulinoopornością i hiperglikemią. W ciągu ostatniej dekady badania CVOT stały się integralną częścią procesu rejestracji leków przeciwcukrzycowych przez Amerykańską Agencję ds. Żywności i Leków (FDA). Większość obecnie stosowanych preparatów insulinowych, poza kilkoma opracowanymi w ostatnich latach insulinami, dopuszczono do obrotu długo przed wprowadzeniem tego wymogu rejestracyjnego, a zatem nie poddano ich rygorystycznym badaniom CVOT. Istnieje wiele danych obserwacyjnych dotyczących sercowo-naczyniowego bezpieczeństwa stosowania preparatów insuliny. Dane te są często niejednoznaczne, a czasami — sprzeczne. W tym kontekście należy zauważyć, że badania CVOT dwóch analogów insuliny bazowej — insuliny glargine ocenianej w badaniu Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia Trial (ORIGIN) i insuliny degludec ocenianej w badaniu Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes Trial (DEVOTE) — wykazały długoterminowe bezpieczeństwo sercowo-naczyniowe ich stosowania. Badanie DEVOTE dostarczyło dodatkowych danych o bezpieczeństwie, wskazujących, że stosowanie insuliny degludec wiązało się z mniejszą liczbą epizodów ciężkiej hipoglikemii niż stosowanie insuliny glargine. Wnioski: W niniejszej pracy dokonano krytycznej analizy dwóch badań CVOT oceniających analogi insuliny bazowej w połączeniu z ogólnym przeglądem meto-dologicznych i interpretacyjnych aspektów badań typu CVOT. Omówiono długoterminowe bezpieczeństwo sercowo-naczyniowe stosowania analogów insuliny bazowej. Za główną lukę badawczą w tej dziedzinie uznano brak badań CVOT z mieszankami insulin ludzkich i analogów insulinowych

Biomimetic electrospun polyurethane matrix composites with tailor made properties for bone tissue engineering scaffolds

Bone tissue scaffolds require appropriate properties conducive for new tissue growth. In this study, we prepared a novel electrospun nanofiber scaffold using polyurethane (PU), rosemary (RM) oil and copper sulphate (CuSO4) respectively. The properties of the developed membranes were established through scanning electron microscopy (FESEM), atomic force microscopy (AFM), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), thermal gravimetric analysis (TGA), contact angle and mechanical testing. Further, blood compatibility and cytocompatibility assay were carried out to evaluate their biological responses. The developed composites rendered appropriate surface morphology with tailor made wettability and roughness. Composites with engineered physicochemical properties improved the blood and cytocompatible properties which can be potentially exploited for bone tissue engineering applications

Manufacturing and characterization of novel electrospun composite comprising polyurethane and mustard oil scaffold with enhanced blood compatibility

The objective of this work is to characterize and investigate the blood compatibility of polyurethane (PU)/mustard oil composites fabricated using electrospinning technique. The fabricated scaffold was characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and contact angle measurements. The activated partial thromboplastin time (APPT), prothrombin time (PT) and the hemolytic assay were done to investigate the blood compatibility of the developed composites. The SEM results revealed that the fiber diameter of the composites (761±123 nm) was reduced compared to pristine PU control. The interaction between PU and mustard oil was confirmed by FTIR as evident through the shifting of peaks. The fabricated composites depicted hydrophobic behavior as insinuated by the increase in contact angle measurements. PU/mustard composites displayed improved crystallinity as confirmed by TGA. Atomic force micrographs suggested that developed PU/mustard oil composites showed an increase in the surface roughness (Ra) compared to pure PU. The Ra of pure PU was observed to be 723 nm but for the fabricated PU/mustard oil composite the Ra was found to be 1298 nm (Ra). The hemolytic index value for pure PU and fabricated composites was observed to be 2.73%and 1.15% indicating that developed composites showed a non-hemolytic behavior signifying the safety of the composites with red blood cells. Hence the newly developed composites with improved physicochemical and blood compatibility properties may be considered as a potential candidate for fabricating cardiac patches and grafts

Folic acid decorated chitosan nanoparticles and its derivatives for the delivery of drugs and genes to cancer cells

Nanotechnology offers a number of nanoscale implements for medicine. Among these, nanoparticles are revolutionizing the field of drug and gene delivery. Chitosan is a natural polymer which provides a profitable tool to an innovative delivery system due to its inherent physicochemical and biological characteristics. Chitosan nanoparticles are promising drug and gene delivery carriers because of small size, better stability, low toxicity, inexpensiveness, simplicity, easy fabrication and versatile means of administration. Chitosan can also be easily modified chemically due to the presence of reactive functional hydroxide and amine groups. Folic acid is commonly engaged as a ligand, for targeting cancer cells, as its receptor, that transports folic acid into the cells through endocytosis and is over-expressed on the surface of several human epithelial cancer cells. Integrating folic acid into chitosan-based drug delivery inventions directs the systems with a well-organized targeting ability. The present review outlines several illustrations of this versatile system based on folate decorated chitosan, which have shown potential as auspicious delivery systems published over the past few years. In addition, it is probable to formulate chitosan nanocarriers that exhibit manifold usage beyond targeted delivery, such as nanotheranostics and cancer stem cell therapy

Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy

The North Star ambulatory assessment (NSAA) is a functional motor outcome measure in Duchenne muscular dystrophy (DMD), widely used in clinical trials and natural history studies, as well as in clinical practice. However, little has been reported on the minimal clinically important difference (MCID) of the NSAA. The lack of established MCID estimates for NSAA presents challenges in interpreting the significance of the results of this outcome measure in clinical trials, natural history studies and clinical practice. Combining statistical approaches and patient perspectives, this study estimated MCID for NSAA using distribution-based estimates of 1/3 standard deviation (SD) and standard error of measurement (SEM), an anchor-based approach, with six-minute walk distance (6MWD) as the anchor, and evaluation of patient and parent perception using participant-tailored questionnaires. The MCID for NSAA in boys with DMD aged 7 to 10 years based on 1/3 SD ranged from 2.3-2.9 points, and that on SEM ranged from 2.9-3.5 points. Anchored on the 6MWD, the MCID for NSAA was estimated as 3.5 points. When the impact on functional abilities was considered using participant response questionnaires, patients and parent perceived a complete loss of function in a single item or deterioration of function in one to two items of the assessment as an important change. Our study examines MCID estimates for total NSAA scores using multiple approaches, including the impact of patient and parent perspective on within scale changes in items based on complete loss of function and deterioration of function, and provides new insight on evaluation of differences in these widely used outcome measure in DMD

NF-κB/Rel-Mediated Regulation of the Neural Fate in Drosophila

Two distinct roles are described for Dorsal, Dif and Relish, the three NF-κB/Rel proteins of Drosophila, in the development of the peripheral nervous system. First, these factors regulate transcription of scute during the singling out of sensory organ precursors from clusters of cells expressing the proneural genes achaete and scute. This effect is possibly mediated through binding sites for NF-κB/Rel proteins in a regulatory module of the scute gene required for maintenance of scute expression in precursors as well as repression in cells surrounding precursors. Second, genetic evidence suggests that the receptor Toll-8, Relish, Dif and Dorsal, and the caspase Dredd pathway are active over the entire imaginal disc epithelium, but Toll-8 expression is excluded from sensory organ precursors. Relish promotes rapid turnover of transcripts of the target genes scute and asense through an indirect, post-transcriptional mechanism. We propose that this buffering of gene expression levels serves to keep the neuro-epithelium constantly poised for neurogenesis

Toll-8/Tollo Negatively Regulates Antimicrobial Response in the Drosophila Respiratory Epithelium

Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP) production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spätzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM). Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium