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PURPOSE:This study was to determine factors associated with individuals presenting late with advanced glaucomatous optic nerve damage. METHODS:A case-control study recruiting 123 patients with early features of primary open angle glaucoma (control) and 93 patients with advanced glaucoma (cases) was carried out for risk-factor analysis. Exposures of interest included those already established as major risk factors for glaucoma. These were initial intraocular pressure (IOP), age, and family history. In addition, occupation, ethnic origin, history of diagnosis of diabetes mellitus, hypertension, sickle cell disease, and previous eye examination were of interest. RESULTS:Univariate analysis showed that initial IOP>31?mmHg, age of>?60years, absence of family history of glaucoma, occupational grouping, ethnicity, and male sex were associated with advanced glaucoma at presentation. Adjusted odds ratio or by multiple logistic regression model showed that initial IOP>31?mmHg in a patient was more likely to present with advanced glaucoma (OR 2.66, 95%confidence interval (CI) 1.45, 4.91; P-value 0.0017) than lower pressures. Patients aged 60-69 years (OR 2.53, 95%CI 1.01, 6.31; P-value 0.0473) and 70-90 years (OR 5.16, 95%CI 1.97, 13.51; P-value 0.0008) were more likely to present with advanced glaucoma than younger ones CONCLUSIONS:Subjects with initial IOP>31?mmHg were nearly three times more likely to present with advanced glaucoma than those with IOP<32?mmHg. Subjects over the age of 60 years were more than two times likely to present with advanced glaucoma than younger subjects.Eye (2005) 19, 528-534. doi:10.1038/sj.eye.6701533 Published online 6 August 2004 [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) is a protozoan parasite that infects all warm-blooded animals including domesticated birds and humans. Birds normally get infected by ground feeding and human beings contract the disease by consumption of undercooked chicken meat. This study aimed to analyze seroprevalence and DNA of T. gondii in chickens (domesticated and broiler) and to assess possible transfer to humans by review of available literature from Pakistan. Blood from and tissues from domesticated and broilers chickens were analyzed for Toxo-IgM/IgG and Toxoplasma DNA through ELISA and PCR respectively. Furthermore, research articles published during 1990-2019 on the prevalence of T. gondii in humans from Pakistan, were analyzed to assess the possible infection burden in the area in connection to transmission from chickens. The overall prevalence of IgM and IgG for T. gondii was 17.83% and 8.8% respectively in the study areas. Significant seroprevalence was found in domesticated chickens than broilers. In domesticated chickens, the prevalence was high in age ≥ 2 years. Toxoplasma DNA was detected in tissues with an overall prevalence of 10.84%. Higher prevalence was observed in liver (10.50%) than heart (9.5%) and muscles (7.11%). Only 4.78% broiler and 2.38% domesticated chickens were positive for both IgM and DNA, 1.2% domesticated and 1.30% broilers were positive for IgG and DNA, while 2.98% domesticated and 2.17% broilers were positive for IgM, IgG, and DNA. Available literature showed that 25.8% of human beings were infected with T. gondii in Pakistan. The prevalence was 20.64% in male and 26.82%in the female. The rate of infections increases with age and high (37.36%) was found in humans of age range 40 to 60 years. A high prevalence of T. gondii is found in both domesticated and broiler chickens in the study area. Moreover, the literature survey indicates that a high seroprevalence of T. gondii is present in human beings of Pakistan. It is concluded that the high prevalence of T. gondii in humans may be associated with the parasite transmission through infected chicken's meat in Pakistan.

Background: Histoplasma capsulatum exposure is rarely suspected in Indonesia. Pulmonary histoplasmosis can occur simultaneously with pulmonary tuberculosis (TB) or as an alternative diagnosis in clinically-diagnosed TB patients with no microbiological evidence of TB. This study aimed to determine the seroprevalence of anti-H. capsulatum IgG antibody among pulmonary TB patients., Methodology: This was a sub-study of 306 participants from a prospective cohort pulmonary TB study conducted at seven TB referral hospitals in Indonesia. The study population was presumptive pulmonary TB adult patients who underwent microbiological TB examinations and were categorized as drug-sensitive (DS), drug-resistant (DR), and clinically-diagnosed TB. Anti-H. capsulatum IgG antibody levels at baseline were measured using MVista Histoplasma Ab enzyme immunoassays. Data were summarized using descriptive statistics. Bivariate and multivariate logistic regression analysis were performed to assess factors associated with anti-H. capsulatum IgG antibody positive result., Results: 12.7% (39/306) of pulmonary TB patients were positive for anti-H. capsulatum IgG antibodies (DR-TB patients (15.9%, 18/114), DS-TB (13.0%, 15/115), and clinically-diagnosed TB (7.8%, 6/77)). The median unit value of anti-H. capsulatum IgG antibody for all positive samples was 15.7 (IQR 10.2-28.9) EU. This median unit value was higher in clinically-diagnosed TB patients compared to DS-TB or DR-TB patients (38.1 (IQR 25.6-46.6) EU, 19.7 (IQR 12.3-28.9) EU, and 10.9 (IQR 9.2-15.4), respectively). There were 10 patients (3.3%) with anti-H. capsulatum IgG antibody levels above 30 EU. Factors associated with the anti-H. capsulatum IgG antibody positive result were malignancies (OR 4.88, 95% CI 1.09-21.69, p = 0.037) and cavitary lesions (OR 2.27, 95% CI 1.09-4.70, p = 0.028)., Conclusions: Our results provide evidence of exposure to H. capsulatum among pulmonary TB patients in Indonesia. Further studies are needed to provide a comprehensive picture of this fungal disease in other populations and regions to enhance awareness among clinicians and public health officials., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kusmiati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Measurement of medial gastrocnemius (MG) tendon length using ultrasonography (US) requires the muscle-tendon junction (MTJ) to be located. Previously, the MG MTJ has been tracked from different proximo-distal locations near the MTJ, which could influence estimates of tendon length change due to the different characteristics of the aponeurosis and tendon. We used US to evaluate the effect of tracking point location on MG MTJ displacement during maximal and submaximal (10, 20 and 30% of the non-injured maximal) isometric plantar flexion contractions., Methods: Displacement behaviour of MTJ was tracked from (1) the exact MTJ; and (2) from an insertion point of a muscle fascicle on the aponeurosis 1.3 ± 0.6 cm proximal to the MTJ, in both limbs of patients with unilateral Achilles tendon rupture (ATR) (n = 22, 4 females, 42 ± 9 years, 177 ± 9 cm, 79 ± 10 kg)., Results: In the non-injured limb, displacement (1.3 ± 0.5 cm vs. 1.1 ± 0.6 cm) and strain (6.7 ± 2.8% vs. 5.8 ± 3.3%) during maximal voluntary contraction were larger when tracking a point on the aponeurosis than when tracking the MTJ (both p < 0.001). The same was true for all contraction levels, and both limbs., Conclusion: Tracking a point on the aponeurosis consistently exaggerates estimates of tendon displacement, and the magnitude of this effect is contraction intensity-dependent. When quantifying displacement and strain of the Achilles tendon, the MTJ should be tracked directly, rather than tracking a surrogate point proximal to the MTJ. The latter method includes part of the aponeurosis, which due to its relative compliance, artificially increases estimates of MTJ displacement and strain., (© 2022. The Author(s).)

Background: Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) has been responsible for the current increase in Coronavirus disease 2019 (COVID-19) infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia. Methods: In this cross-sectional study, we ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole-genome sequences of SARS-CoV-2. Results: The mean age of patients with the Delta variant and the non-Delta variant was 27.3 ± 20.0 and 43.0 ± 20.9 ( p = 3 × 10 -6 ). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females ( p = 0.001). The Ct value of the Delta variant (18.4 ± 2.9) was significantly lower than that of the non-Delta variant (19.5 ± 3.8) ( p = 0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants ( p = 0.80 and 0.29, respectively). None of the prognostic factors were associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI = 1.02-12.5; p = 0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than the patients without the factors: age ≥65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI = 3.4-36; p = 8 × 10 -5 ), 27 (95% CI = 6.1-118; p = 1 × 10 -5 ), 15.6 (95% CI = 5.3-46; p = 6 × 10 -7 ), 12 (95% CI = 4-35.3; p = 1.2 × 10 -5 ), and 6.8 (95% CI = 2.1-22.1; p = 0.003), respectively. Multivariate analysis showed that age ≥65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI = 0.58-21.9; p = 0.028), 16.6 (95% CI = 2.5-107.1; p = 0.003), 5.5 (95% CI = 1.3-23.7; p = 0.021), and 5.8 (95% CI = 1.02-32.8; p = 0.047), respectively. Conclusions: We show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms that older age and comorbidity increase the mortality rate of patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gunadi, Hakim, Wibawa, Marcellus, Setiawaty, Slamet, Trisnawati, Supriyati, El Khair, Iskandar, Afiahayati, Siswanto, Irene, Anggorowati, Daniwijaya, Nugrahaningsih, Puspadewi, Puspitarani, Tania, Vujira, Ardlyamustaqim, Gabriela, Eryvinka, Nirmala, Geometri, Darutama, Kuswandani, Lestari, Irianingsih, Khoiriyah, Lestari, Ananda, Arguni, Nuryastuti and Wibawa.)

Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( r  = -0.61), deceleration time ( r  = 0.75), longitudinal systolic to diastolic time ratio ( r  = 0.59), early diastolic strain rate ( r  = -0.5), circumferential peak atrial-diastolic strain rate ( r  = -0.52), and deceleration time ( r  = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH., (© The Author(s) 2021.)

The purpose of this study was investigate tendon displacement patterns in non-surgically treated patients 14 months after acute Achilles tendon rupture (ATR) and to classify patients into groups based on their Achilles tendon (AT) displacement patterns. Twenty patients were tested. Sagittal images of AT were acquired using B-mode ultrasonography during ramp contractions at a torque level corresponding to 30% of the maximal isometric plantarflexion torque of the uninjured limb. A speckle tracking algorithm was used to track proximal-distal movement of the tendon tissue at 6 antero-posterior locations. Two-way repeated measures ANOVA for peak tendon displacement was performed. K-means clustering was used to classify patients according to AT displacement patterns. The difference in peak relative displacement across locations was larger in the uninjured (1.29 ± 0.87 mm) than the injured limb (0.69 ± 0.68 mm), with a mean difference (95% CI) of 0.60 mm (0.14-1.05 mm, P < .001) between limbs. For the uninjured limb, cluster analysis formed 3 groups, while 2 groups were formed for the injured limb. The three distinct patterns of AT displacement during isometric plantarflexion in the uninjured limb may arise from subject-specific anatomical variations of AT sub-tendons, while the two patterns in the injured limb may reflect differential recovery after ATR with non-surgical treatment. Subject-specific tendon characteristics are a vital determinant of stress distribution across the tendon. Changes in stress distribution may lead to variation in the location and magnitude of peak displacement within the free AT. Quantifying internal tendon displacement patterns after ATR provides new insights into AT recovery., (© 2021 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: Prolonged nucleic acid conversion and false-negative real-time polymerase chain reaction (RT-PCR) results might occur in COVID-19 patients rather than infection recurrence., Presentation of Cases: We reported four cases who had negative RT-PCR results, in addition to the last two consecutive negative results. Patient-1 had negative RT-PCR results twice (the 6th and 8th) from a total of 11 swabs. Patient-2 had negative RT-PCR results once (the 5th) from a total of 8 swabs. Patient-3 showed negative results of RT-PCR twice (the 4th and 6th) from a total of 11 swabs. Patient-4 had negative RT-PCR results twice (the 2nd and 10th) from a total of 14 swabs., Discussion: The fluctuating trend of our RT-PCR results in our cases might be due to insufficient viral material in the specimen, laboratory errors during sampling, restrictions on sample transportation, or mutations in the primary and probe target regions in the SARS-CoV-2 genome. Several factors might affect the occurrence of prolonged nucleic acid conversion, including older age, comorbidities, such as diabetes and hypertension, and impaired immune function., Conclusion: Here, we confirmed the occurrence of prolonged nucleic acid conversion and the possibility of false negative RT-PCR results in COVID-19 patients., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Among lipid-based nanocarriers, multi-layered cochleates emerge as a novel delivery system because of prevention of oxidation of hydrophobic and hydrophilic drugs, enhancement in permeability, and reduction in dose of drugs. It also improves oral bioavailability and increases the safety of a drug by targeting at a specific site with less side effects. Nanostructured cochleates are used as a carrier for the delivery of water-insoluble or hydrophobic drugs of anticancer, antiviral and anti-inflammatory action. This review article focuses on different methods for preparation of cochleates, mechanism of formation of cochleates, mechanism of action like cochleate undergoes macrophagic endocytosis and release the drug into the systemic circulation by acting on membrane proteins, phospholipids, and receptors. Advanced methods such as calcium-substituted and β-cyclodextrin-based cochleates, novel techniques include microfluidic and modified trapping method. Cochleates showed enhancement in oral bioavailability of amphotericin B, delivery of factor VII, oral mucosal vaccine adjuvant-delivery system, and delivery of volatile oil. In near future, cochleate will be one of the interesting delivery systems to overcome the stability and encapsulation efficiency issues associated with liposomes. The current limiting factors for commercial preparation of cochleates involve high cost of manufacturing, lack of standardization, and specialized equipments.

The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH). Twenty-one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow-up. Increased 6-min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N-terminal pro-brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR-derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.).

Background: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH., Methods: In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints., Results: At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05)., Conclusions: Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).