Advanced Glycation End Products Upregulate CD40 in Human Retinal Endothelial and Müller Cells: Relevance to Diabetic Retinopathy.

CD40 induces pro-inflammatory responses in endothelial and Müller cells and is required for the development of diabetic retinopathy (DR). CD40 is upregulated in these cells in patients with DR. CD40 upregulation is a central feature of CD40-driven inflammatory disorders. What drives CD40 upregulation in the diabetic retina remains unknown. We examined the role of advanced glycation end products (AGEs) in CD40 upregulation in endothelial cells and Müller cells. Human endothelial cells and Müller cells were incubated with unmodified or methylglyoxal (MGO)-modified fibronectin. CD40 expression was assessed by flow cytometry. The expression of ICAM-1 and CCL2 was examined by flow cytometry or ELISA after stimulation with CD154 (CD40 ligand). The expression of carboxymethyl lysine (CML), fibronectin, and laminin as well as CD40 in endothelial and Müller cells from patients with DR was examined by confocal microscopy. Fibronectin modified by MGO upregulated CD40 in endothelial and Müller cells. CD40 upregulation was functionally relevant. MGO-modified fibronectin enhanced CD154-driven upregulation of ICAM-1 and CCL2 in endothelial and Müller cells. Increased CD40 expression in endothelial and Müller cells from patients with DR was associated with increased CML expression in fibronectin and laminin. These findings identify AGEs as inducers of CD40 upregulation in endothelial and Müller cells and enhancers of CD40-dependent pro-inflammatory responses. CD40 upregulation in these cells is associated with higher CML expression in fibronectin and laminin in patients with DR. This study revealed that CD40 and AGEs, two important drivers of DR, are interconnected.

A thorough Investigation of Rare-Earth Dy3+ Substituted Cobalt-Chromium Ferrite and Its Magnetoelectric Nanocomposite.

The stoichiometric compositions of a ferrite system with a chemical formula CoCr0.5DyxFe1.5-xO4 where x = 0.0, 0.025, 0.05, 0.075 and 0.1 were prepared by the sol-gel auto-combustion method. The structural, morphological and magnetic properties were studied by the X-ray diffraction (XRD), infra-red spectroscopy (IR), scanning electron microscopy, transmission electron microscopy and vibrating sample magnetometer. XRD analysis confirmed the cubic spinel structure of the prepared samples without the presence of any impurity and secondary phases. Selected area electron diffraction and IR measurements gives further confirmation to the XRD observations. Considering that strain mechanism, elastic properties and cation distribution play a major role for controlling the magnetic properties and therefore these properties were precisely evaluated through reliable methodologies such as XRD and IR data. The cation distribution was determined by the X-ray diffraction data which are further supported by the magnetization studies. Magnetoelectric properties of CoCr0.5DyxFe1.5-xO4 + BaTiO3 have also been investigated. The mechanisms involved are discussed in the manuscript.

Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia.

With aging, human lenses lose the ability to focus on nearby objects due to decreases in accommodative ability, a condition known as presbyopia. An increase in stiffness or decrease in lens elasticity due to protein aggregation and insolubilization are the primary reasons for presbyopia. In this study, we tested aggrelyte-1 (S,N-diacetyl glutathione diethyl ester) for its ability to promote protein solubility and decrease the stiffness of lenses through its dual property of lysine acetylation and disulfide reduction. Treatment of water-insoluble proteins from aged human lenses (58-75 years) with aggrelyte-1 significantly increased the solubility of those proteins. A control compound that did not contain the S-acetyl group (aggrelyte-1C) was substantially less efficient in solubilizing water-insoluble proteins. Aggrelyte-1-treated solubilized protein had significant amounts of acetyllysine, as measured by Western blotting and LC-MS/MS. Aggrelytes increased the protein-free thiol content in the solubilized protein. Aged mouse (7 months) and human (44-66 years) lenses treated with aggrelyte-1 showed reduced stiffness accompanied by higher free thiol and acetyllysine levels compared with those treated with aggrelyte-1C or untreated controls. Our results suggested that aggrelyte-1 reduced lens stiffness through acetylation followed by disulfide reduction. This proof-of-concept study paves the way for developing aggrelyte-1 and related compounds to reverse presbyopia.

Aggrelyte-2 promotes protein solubility and decreases lens stiffness through lysine acetylation and disulfide reduction: Implications for treating presbyopia.

Aging proteins in the lens become increasingly aggregated and insoluble, contributing to presbyopia. In this study, we investigated the ability of aggrelyte-2 (N,S-diacetyl-L-cysteine methyl ester) to reverse the water insolubility of aged human lens proteins and to decrease stiffness in cultured human and mouse lenses. Water-insoluble proteins (WI) of aged human lenses (65-75 years) were incubated with aggrelyte-2 (500 µM) for 24 or 48 h. A control compound that lacked the S-acetyl group (aggrelyte-2C) was also tested. We observed 19%-30% solubility of WI upon treatment with aggrelyte-2. Aggrelyte-2C also increased protein solubility, but its effect was approximately 1.4-fold lower than that of aggrelyte-2. The protein thiol contents were 1.9- to 4.9-fold higher in the aggrelyte-2- and aggrelyte-2C-treated samples than in the untreated samples. The LC-MS/MS results showed Nε -acetyllysine (AcK) levels of 1.5 to 2.1 nmol/mg protein and 0.6 to 0.9 nmol/mg protein in the aggrelyte-2- and aggrelyte-2C-treated samples. Mouse (C57BL/6J) lenses (incubated for 24 h) and human lenses (incubated for 72 h) with 1.0 mM aggrelyte-2 showed significant decreases in stiffness with simultaneous increases in soluble proteins (human lenses) and protein-AcK levels, and such changes were not observed in aggrelyte-2C-treated lenses. Mass spectrometry of the solubilized protein revealed AcK in all crystallins, but more was observed in α-crystallins. These results suggest that aggrelyte-2 increases protein solubility and decreases lens stiffness through acetylation and disulfide reduction. Aggrelyte-2 might be useful in treating presbyopia in humans.

Psychodermatology - a case for sensitization of pharmacists in Mumbai, India.

BACKGROUND: Though studies have looked at the attitudes of dermatologists towards psychodermatology, few have highlighted the attitudes of pharmacists towards these conditions. OBJECTIVES: To study the knowledge, attitudes and practices of pharmacists towards the prescription of psychotropic medications to dermatology patients. METHODS: This cross-sectional analysis included 80 pharmacists from Mumbai, India. We used an interviewer-administered questionnaire to collect information from pharmacists on their demographics, psychotropic medications in dermatological patients, knowledge about psychocutaneous conditions and comfort about dispensing these medications. RESULTS: In our study, 37 (46%) of pharmacists received prescriptions of psychotropic drugs from dermatologists; however, 24 (30%) were not comfortable dispensing them. Sixty (75%) pharmacists felt that only psychiatrists should prescribe psychotropic drugs and 37 (46%) felt that they had a right to refuse to dispense prescribed medication; of these, 15 (19%) had actually refused to give medications to patients. Pharmacists who disagreed with the statement that 'the state of mind is associated with medical conditions', were more likely to discourage psychotropic prescription from dermatologists (29% vs 11%, P = 0.04). Pharmacists with experience of more than five years were significantly more likely to refuse to dispense medications (odds ratio: 5.14, 95% confidence interval: 1.02, 25.83; P = 0.047). LIMITATIONS: We did not have a list of all pharmacists in Mumbai; thus, no sampling frame could be applied. CONCLUSION: Pharmacists do comment on doctors' prescriptions, discourage certain medications and even refuse to dispense them based on their personal opinions. Since they are the last stop for patients between the doctor and the medication, their inclusion (in addition to dermatologists, psychiatrists and psychologists) in integrated awareness, training and care programs would improve the quality of care of patients with psychocutaneous disorders.

Peptains block retinal ganglion cell death in animal models of ocular hypertension: implications for neuroprotection in glaucoma.

Ocular hypertension is a significant risk factor for vision loss in glaucoma due to the death of retinal ganglion cells (RGCs). This study investigated the effects of the antiapoptotic peptides peptain-1 and peptain-3a on RGC death in vitro in rat primary RGCs and in mouse models of ocular hypertension. Apoptosis was induced in primary rat RGCs by trophic factor deprivation for 48 h in the presence or absence of peptains. The effects of intravitreally injected peptains on RGC death were investigated in mice subjected to retinal ischemic/reperfusion (I/R) injury and elevated intraocular pressure (IOP). I/R injury was induced in mice by elevating the IOP to 120 mm Hg for 1 h, followed by rapid reperfusion. Ocular hypertension was induced in mice by injecting microbeads (MB) or silicone oil (SO) into the anterior chamber of the eye. Retinal flatmounts were immunostained with RGC and activated glial markers. Effects on anterograde axonal transport were determined by intravitreal injection of cholera toxin-B. Peptain-1 and peptain-3a inhibited neurotrophic factor deprivation-mediated RGC apoptosis by 29% and 35%, respectively. I/R injury caused 52% RGC loss, but peptain-1 and peptain-3a restricted RGC loss to 13% and 16%, respectively. MB and SO injections resulted in 31% and 36% loss in RGCs following 6 weeks and 4 weeks of IOP elevation, respectively. Peptain-1 and peptain-3a inhibited RGC death; the loss was only 4% and 12% in MB-injected eyes and 16% and 15% in SO-injected eyes, respectively. Anterograde transport was defective in eyes with ocular hypertension, but this defect was substantially ameliorated in peptain-injected eyes. Peptains suppressed ocular hypertension-mediated retinal glial activation. In summary, our results showed that peptains block RGC somal and axonal damage and neuroinflammation in animal models of glaucoma. We propose that peptains have the potential to be developed as therapeutics against neurodegeneration in glaucoma.

Quercitrin neutralizes sPLA2IIa activity, reduces the inflammatory IL-6 level in PC3 cell lines, and exhibits anti-tumor activity in the EAC-bearing mice model.

Human phospholipase A2 group IIa (sPLA2IIa) is an inflammatory enzyme that plays a significant role in tumorigenesis. Inhibiting the sPLA2IIa enzyme with an effective molecule can reduce the inflammatory response and halt cancer progression. The present study evaluates quercitrin, a biflavonoid, for sPLA2IIa inhibition and anticancer activity. Quercitrin inhibited sPLA2IIa activity to a greater extent-at 86.24% ± 1.41 with an IC50 value of 8.77 µM ± 0.9. The nature of sPLA2IIa inhibition was evaluated by increasing calcium concentration from 2.5 to 15 µM and substrate from 20 to 120 nM, which did not alter the level of inhibition. Intrinsic fluorescence and far UV-CD studies confirmed the direct interaction of quercitrin with the sPLA2IIa enzyme. This significantly reduced the sPLA2IIa-induced hemolytic activity and mouse paw edema from 97.32% ± 1.23-16.91% ± 2.03 and 172.87% ± 1.9-118.41% ± 2.53, respectively. As an anticancer activity, quercitrin reduced PC-3 cell viability from 98.66% ± 2.51-18.3% ± 1.52 and significantly decreased the IL-6 level in a dose-dependent manner from 98.35% ± 2.2-37.12% ± 2.4. It increased the mean survival time (MST) of EAC-bearing Swiss albino mice from 30 to 35 days. It obeyed Lipinski's rule of five, suggesting a druggable property. Thus, all the above experimental results were promising and encouraged further investigation into developing quercitrin as a therapeutic drug for both inflammatory diseases and cancers.

Migratory Panniculitis with Autoimmune Cholangitis and Pancreatitis (IgG4- Related Disease): A Rare Presentation.

A 30-year-old woman presented with an acute-onset high-grade fever (103°F), multiple episodes of throbbing abdominal pain in the right quadrant, and pustular red lesions on the left leg. The radiological findings were suggestive of autoimmune cholangitis and pancreatitis. The skin lesions recurred on different portions of the body, and histopathological findings showed lobular and septal lymphohistiocytic infiltrate without vasculitis. The epidermis had focal ulcerations, and the dermis showed the presence of subcutaneous fat and an infiltrate of lymphocytes, histiocytes, and neutrophils (described as lobular and septal panniculitis without vasculitis). Based on the clinical and histopathological features, a diagnosis of migratory panniculitis was made. The patient was managed with analgesics, antibiotics, and a long course of steroids; the patient responded well to these medications. To the best of our knowledge, this is one of the first case reports of migratory panniculitis associated with IgG4-related disease. Patients with migratory panniculitis should be investigated for the presence of IgG4-related autoimmune disease. However, steroids remain the drug of choice when these conditions occur together.

AAV2-Mediated Expression of HspB1 in RGCs Prevents Somal Damage and Axonal Transport Deficits in a Mouse Model of Ocular Hypertension.

Purpose: Ocular hypertension is a significant risk factor for vision loss in glaucoma caused by the death of retinal ganglion cells (RGCs). We investigated whether small heat shock proteins (sHsps) expressed in RGCs protect those cells against ocular hypertension in mice. Methods: AAV2 vectors encoding genes for one of the following four human sHsps: HSPB1, HSPB4, HSPB5, or HSPB6 were constructed for RGC-specific expression. Ischemia/reperfusion was induced by elevating the intraocular pressure (IOP) to 120 mm Hg for one hour, followed by a rapid return to normal IOP. Microbeads (MB) were injected into the anterior chamber of mice to induce ocular hypertension. RGC death and glial activation were assessed by immunostaining for Brn3a, RBPMS, Iba1, and glial fibrillary acid protein in retinal flat mounts. RGC axonal defects were evaluated by anterograde transport of intravitreally injected cholera toxin-B. RGC function was assessed by pattern electroretinography. Results: Among the sHsps, HspB1 offered the best protection against RGC death from ischemia/reperfusion injury in the mouse retina. Intravitreal administration of AAV2-HSPB1 either two weeks before or one week after instituting ocular hypertension resulted in significant prevention of RGC loss. The MB-injected mice showed RGC axonal transportation defects, but AAV2-HSPB1 administration significantly inhibited this defect. AAV2-HSPB1 prevented glial activation caused by ocular hypertension. More importantly, a single injection of AAV2-HSPB1 protected RGCs long-term in MB-injected eyes. Conclusions: The administration of AAV2-HSPB1 inhibited RGC death and axonal transport defects and reduced glial activation in a mouse model of ocular hypertension. Translational Relevance: Our results suggested that the intravitreal delivery of AAV2-HSPB1 could be developed as a gene therapy to prevent vision loss on a long-term basis in glaucoma patients.

Massive haemoptysis in a woman with left lower lobe pulmonary artery interruption-A rare clinical presentation.

Proximal interruption of the pulmonary artery (PA) is a rare congenital vascular anomaly with varying presentation. These patients can be asymptomatic or symptomatic with breathlessness, haemoptysis, recurrent chest infections and pulmonary hypertension. Here, we present a patient who presented with massive haemoptysis secondary to interruption of the left lower lobe PA. To the best of our knowledge, massive haemoptysis due to isolated interruption of the left lower lobe PA has been rarely reported in the English medical literature.

Small Heat Shock Proteins in Retinal Diseases.

This review summarizes the latest findings on small heat shock proteins (sHsps) in three major retinal diseases: glaucoma, diabetic retinopathy, and age-related macular degeneration. A general description of the structure and major cellular functions of sHsps is provided in the introductory remarks. Their role in specific retinal diseases, highlighting their regulation, role in pathogenesis, and possible use as therapeutics, is discussed.

Comparison and outcomes of emergency department presentations with respiratory disorders among Australian indigenous and non-indigenous patients.

BACKGROUND: There is sparse evidence in the literature assessing emergency department presentation with respiratory disorders among Indigenous patients. The objective of this study was to evaluate the clinical characteristics and outcomes for Indigenous Australians in comparison to non-Indigenous patients presenting to Emergency Department (ED) with respiratory disorders. METHODS: In this study, two non-contiguous one-month study periods during wet (January) and dry (August) season were reported on, and differences in demographics, respiratory diagnosis, hospital admission, length of hospital stay, re-presentation to hospital after discharge and mortality between Australian Indigenous and non-Indigenous patients was assessed. RESULTS: There were a total of 528 respiratory ED presentations, 258 (49%) during wet and 270 (51%) in dry season, from 477 patients (52% female and 40% Indigenous). The majority of ED presentations (84%) were self-initiated, with a difference between Indigenous (80%) and non-Indigenous (88%) presentations. Indigenous presentations recorded a greater proportion of transfers from another healthcare facility compared to non-Indigenous presentations (11% vs. 1%). Less than half of presentations (42%) resulted in admission to the ward with no difference by Indigenous status. Lower respiratory tract infections were the most common cause of presentation (41%), followed by airway exacerbation (31%) which was more commonly seen among Indigenous (34%) than non-Indigenous (28%) presentations. Almost 20% of Indigenous patients reported multiple presentations to ED compared to 1% of non-Indigenous patients, though mortality on follow up did not differ (22% for both). CONCLUSIONS: The results of this study may be an avenue to explore possibilities of implementing programs that may be helpful to reduce preventable ED presentation and recurrent hospitalisations among Indigenous population.

Associations between breast implants and postpartum lactational mastitis in breastfeeding women: retrospective study.

OBJECTIVE: To examine the putative associations between breast implants and postpartum lactational mastitis. DESIGN: Observational retrospective study. SETTING: Digital database of Maccabi Healthcare Services, integrated health maintenance organisation in Israel. POPULATION: Breastfeeding mothers from 2003 to 2016 based on an initial health maintenance organisation data set of 28 383 singleton live births in Israel. METHODS: Multivariate analysis and propensity score matching were used to test the extent to which breast implants were associated with lactational mastitis during the 6-month postpartum period in breastfeeding mothers. Analyses for potential confounders were adjusted for socio-economic status, smoking and parity. MAIN OUTCOME MEASURE: Lactational mastitis among breastfeeding women with breast implants compared with women without breast implants. RESULTS: Mothers with breast implants (n = 6099) were significantly (P < 0.001) more likely to be diagnosed with postpartum mastitis (8.3%) than mothers with no breast implants(n = 22 284) (6.6%) at an odds ratio of 1.22 (95% CI 1.09-1.35) after adjusting for confounders. CONCLUSION: Breast augmentation is associated with an increased risk of postpartum lactational mastitis in the 6-month postpartum period. In light of these findings, it is important for health professionals to instruct women who have undergone breast augmentation on correct breastfeeding techniques, ways to avoid risk factors, and to be alert to signs permitting the early detection of lactational mastitis. TWEETABLE ABSTRACT: A study of over 28,000 breastfeeding women has shown that breast augmentation is associated with an increased risk of postpartum lactational mastitis in the six-month postpartum period.

In vitro immuno-stimulatory and anticancer activities of Oroxylum indicum (L.) Kurz.: An evidence for substitution of aerial parts for conservation.

BACKGROUND: In Ayurveda, "Dashamoolarishta" is one of the important composite herbal formulations. Mainly, the root and root bark of Oroxylum indicum are used as one of the ingredients in its preparation. This leads to over exploitation of medicinal plants owing, to excessive demand due to population expansion and its perceived importance in traditional herbal remedies. OBJECTIVE: For the conservation of biodiversity, the present investigation had an objective to prepare the extracts of different parts of O. indicum plant and to, compare the chemo-profiles as well as to study the biological activities of the prepared extracts. MATERIALS AND METHODS: Hydro-alcoholic (HA) and aqueous (Aq) extracts of various plant parts were prepared and chemical investigation was done with the help of (LC-MS/MS). Further, in vitro biological activities such as immuno-stimulation (IS) using a cytokine bioassay in RAW264.7 and in vitro anticancer in TNF-α ELISA in THP-1 cells were studied. RESULTS: The mass spectral profile of the plant revealed the presence of markers such as oroxylin A and chrysin in HA and Aq extracts of stem, leaf, bark and root. Cytokine release and TNF-α secretion was observed in both hydro-alcoholic and aqueous extracts. CONCLUSION: Based on the results from the present study, it can be concluded that it is possible to replace the roots and the bark of O. indicum with the stem of young plants and leaves. It paves a way for the conserving the medicinal plants without uprooting and extinguishing the whole plant.

Advanced glycation end products in human diabetic lens capsules.

Advanced glycation end products (AGEs) accumulate with age in human lens capsules. AGEs in lens capsules potentiate the transforming growth factor beta-2-mediated mesenchymal transition of lens epithelial cells, which suggests that they play a role in posterior capsule opacification after cataract surgery. We measured AGEs by liquid chromatography-mass spectrometry in capsulorhexis specimens obtained during cataract surgery from nondiabetic and diabetic patients with and without established retinopathy. Our data showed that the levels of most AGEs (12 out of 13 measured) were unaltered in diabetic patients and diabetic patients with retinopathy compared to nondiabetic patients. There was one exception: glucosepane, which was significantly higher in diabetic patients, both with (6.85 pmol/µmol OH-proline) and without retinopathy (8.32 pmol/µmol OH-proline), than in nondiabetic patients (4.01 pmol/µmol OH-proline). Our study provides an explanation for the similar incidence of posterior capsule opacification between nondiabetic and diabetic cataract patients observed in several studies.

Transforming growth factor-ß2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE.

Transforming growth factor-ß2 (TGFß2)-mediated epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs) has been implicated in fibrosis associated with secondary cataracts. In this study, we investigated whether the receptor for advanced glycation end products (RAGE) plays a role in TGFß2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGFß2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGFß2-mediated Smad signaling. In addition, treatment with TGFß2 increased IL-6 levels in LECs from wild-type mice but not in those from RAGE knockout mice. Treatment of human LECs with the RAGE inhibitor FPS-ZM1 reduced TGFß2-mediated Smad signaling and the EMT response. Unlike that in wild-type lenses, the removal of fiber cell tissue in RAGE knockout lenses did not result in elevated levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin ß1 in capsule-adherent LECs. Taken together, these results suggest that TGFß2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.

Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro.

Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.

Transient elevation of temperature promotes cross-linking of α-crystallin-client proteins through formation of advanced glycation endproducts: A potential role in presbyopia and cataracts.

The chaperone activity of α-crystallin is important for maintaining the transparency of the human lens. αB-crystallin (αBC) is a long-lived protein in the lens that accumulates chemical modifications during aging. The formation of advanced glycation end products (AGEs) through glycation is one such modification. αBC is a small heat shock protein that exhibits chaperone activity. We have previously shown that αBC-client protein complexes can undergo AGE-mediated interprotein cross-linking. Here, we demonstrate that short-term (1 h) exposure to elevated temperatures and methylglyoxal (MGO) during the chaperoning of client proteins by αBC promotes AGE-mediated interprotein cross-linking. Liquid chromatography/mass spectrometry (LC-MS/MS) analyses revealed the rapid formation of AGEs by MGO. Interestingly, we found that despite protein cross-linking, the chaperone activity of αBC increased during the transient elevation of temperature in the presence of MGO. Together, these results imply that transient and subtle elevation of temperature in the lens of the eye can promote protein cross-linking through AGEs, and if this phenomenon recurs over a period of many years, it could lead to early onset of presbyopia and age-related cataracts.

Gender Differences in the Clinical and Polysomnographic Characteristics Among Australian Aboriginal Patients with Obstructive Sleep Apnea.

BACKGROUND: In this study, we assessed the clinical and polysomnographic (PSG) characteristics according to gender among Australian Aboriginal men and woman diagnosed to have obstructive sleep apnea (OSA). METHODS: In this retrospective study, all adult Aboriginal patients over 18 years of age diagnosed to have OSA with an apnea hypopnea index (AHI) > 5/hour over a 5 year period were included. RESULTS: Of the 337 patients (168 females and 169 males), who underwent a diagnostic PSG, 297 (88%) were diagnosed to have OSA (AHI) >5/hour), 154/297 males (52%) and 143/297 females (48%). Amongst male and female patients with OSA, 63% and 37% were in the severe spectrum (AHI>30/hour). The male cohort had higher stage N1 NREM sleep (P<0.001), reduced N3 NREM sleep (P<0.001), higher AHI severity (P<0.001), higher NREM AHI (P<0.001), and high arousal index (P<0.005). REM sleep-related AHI was higher among female patients with all severity of OSA, along with severe oxygen desaturation during REM sleep. Among patients with severe OSA, the female cohort were younger (age 46 years vs 49 years, P=0.030) and had higher BMI with all severity of OSA, while males had larger neck circumference compared to females. Hypertension increased the odds of severe OSA versus the combined odds of mild and moderate OSA for both genders. CONCLUSION: This study highlights some important differences in the way sleep apnea manifests in Australian Aboriginal males and females and further studies are warranted to explore avenues to look for a physiological basis for these observations and targeted interventions.