Next-to-Next-to-Leading Order QCD Corrections to Semi-Inclusive Deep-Inelastic Scattering.

We present the first results for the next-to-next-to leading order (NNLO) corrections to the semi-inclusive deep-inelastic scattering process in perturbative quantum chromodynamics. We consider the quark initiated flavor nonsinglet process and obtain the complete contributions analytically at leading color. All relevant virtual and real emission Feynman diagrams have been computed using integration-by-parts reduction to master integrals and two approaches for their subsequent evaluation (parametric phase-space integration and method of differential equations). The numerical analysis demonstrates the significance of the NNLO corrections and their great impact on the reduction of the residual scale dependence.

MRI Findings and Topographic Distribution of Lesions in Metronidazole-Induced Encephalopathy.

Purpose This study aims to describe the magnetic resonance imaging (MRI) of the brain of five patients diagnosed with metronidazole-induced encephalopathy (MIE). In addition, the aim of our study was to better define the topographic distribution of lesions in MIE. Methods We retrospectively evaluated MRI findings before and after drug cessation in five patients diagnosed with MIE at Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India. The main MRI signal changes and lesion locations were studied. Results Among the patients observed, the average age of the patients with MIE was 55 years (range: 30-70 years). Cerebellar dysfunction, mainly ataxia, and altered mental status were seen in the majority of cases. The most frequently involved sites were the dentate nucleus (cerebellum), brain stem, and corpus callosum (splenium). In diffusion-weighted imaging (DWI), most lesions did not show true restricted diffusion, except for a solitary corpus callosum lesion. Conclusion Although drug-related side effects are more common with long-term use of metronidazole, they may also occur with high doses for short durations. The dentate nucleus, the splenium in the corpus callosum, and the brain stem are the most affected structures. Apart from a solitary lesion of the corpus callosum, all identified lesions were reversible at follow-up MRI after discontinuation of metronidazole. The clinical presentation and characteristic MRI changes are highly specific and can be correlated to make a rapid and more accurate diagnosis of this potentially treatable condition. Prognosis is excellent if detected early.

Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin.

PURPOSE: Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability. METHODS: The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels - 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy. RESULTS: Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin. CONCLUSIONS: The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be the result of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.

Association and Correlation Between Amniotic Fluid Index and Glucose Concentration.

PURPOSE: To study the association and correlation between the amniotic fluid index, random glucose concentration, and serum glucose concentration after avoiding oral intake of sugar in a pregnant female with polyhydramnios. METHODS: The research was performed on pregnant women with polyhydramnios (n=104 ) after 28 weeks. USG was performed using a SAMSUNG HS 70A (Samsung Electronics Pvt. Ltd., Seoul, South Korea) and a GE Voluson P8 (GE Healthcare, Little Chalfont, UK). We measured amniotic fluid index and took a blood sample for hemoglobin (Hb)A1C, fasting blood glucose, post-prandial and random blood glucose, and also performed a glucose tolerance test in pregnant women. RESULTS: This is a prospective study, all 104 patients that were recruited in this study were pregnant females with polyhydramnios mainly from the urban and rural zone with different age groups (between 21 and 37 years). In our study, we observed that after avoiding oral intake of sugar in pregnant females with polyhydramnios, it was concluded that the amnionic fluid index lies towards the lower side. Polyhydramnios is more common in the urban zone and among older pregnant females. Out of 104 pregnant females with polyhydramnios, 82 were diagnosed with gestational diabetes after 28 weeks. CONCLUSION: In this study, we have concluded that the earliest and most sensitive predictor for gestational diabetes is a rise in the amniotic fluid index which could have been prevented by avoiding oral intake of sugar. Early prediction of gestational diabetes can be made by amniotic fluid index even before glucose concentration. We observed that by reducing oral intake of sugar, the amniotic fluid index drops down in pregnant females.

Prevalence of Insulin Resistance in Type 1 Diabetes Mellitus and Its Correlation with Metabolic Parameters: The Double Trouble.

OBJECTIVE: The phenotype of type 1 diabetes mellitus has changed over the last few decades. Little attention has been paid to the presence of insulin resistance in individuals with type 1 diabetes mellitus. The appearance of insulin resistance in type 1 diabetes mellitus patients has been labeled as "double diabetes." This phenotype of double diabetes has been seen to have higher rate of microvascular as well as macrovascular complica- tions. The aim of the current study was to estimate the burden of insulin resistance in patients with type 1 diabetes mellitus and its correlation with various metabolic parameters and microvascular complications. MATERIALS AND METHODS: It was a cross-sectional study in which a total of 95 type 1 diabetes mellitus patients (children/adolescents (<18 years) and adults ≥18 years) presenting to Endocrinology OPD were screened for the presence of insulin resistance using estimated glucose disposal rate. Estimated glucose disposal rate (mg/kg/min) was calculated as = 21.16- (0.09 ×WC) - (3.407×HTN) - (0.551×HbA1c [%]) where, WC is waist circumference (cm) and HTN is hypertension (1= yes, 0 = no). Based on previous studies, an estimated glucose disposal rate <8 was considered to have the presence of insulin resistance and double diabetes. RESULTS: Using an estimated glucose disposal rate <8 as the cut-off for the presence of insulin resistance, the overall prevalence was 16.8%. Prevalence was high in adults 12 (29.3%) compared to children/adolescents 4 (7.4%) which was statistically significant [χ2 = 7.95; P = .004]. In comparison of the anthropometric and metabolic parameters in those with an estimated glucose disposal rate <8 versus ≥8, there was a significant statistical difference. Those having an estimated glucose disposal rate <8 had higher age, longer duration of diabetes, and body mass index [P ≤ .05]. Also, they had poor glycemic control, higher blood pressure, triglycerides, low-density lipoproteins levels. Using Spearman correlation coefficient there was a statistically significant (P < .05) negative correlation between the estimated glucose disposal rate and various anthropo- metric as well as metabolic parameters. CONCLUSION: This study shows that with increasing duration of disease, insulin resistance (low estimated glucose disposal rate) could be a serious problem in type 1 diabetes mellitus patients, especially in those who are metabolically unhealthy. As insulin resistance could be a major contributing factor in the onset and progression of various vascular complications, evaluation of the presence of insulin resistance using estimated glucose disposal rate could be useful in recognizing individuals who would benefit the most from preventa- tive strategies.

Effect of Storage Humidity on Physical Stability of Spray-Dried Naproxen Amorphous Solid Dispersions with Polyvinylpyrrolidone: Two Fluid Nozzle vs. Three Fluid Nozzle.

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

Effect of Polymer Species on Maximum Aqueous Phase Supersaturation Revealed by Quantitative Nuclear Magnetic Resonance Spectroscopy.

The polymer used in an amorphous solid dispersion (ASD) formulation impacts the maximum achievable drug supersaturation. Herein, the effect of dissolved polymer on drug concentration in the aqueous phase when a drug-rich phase was generated by liquid-liquid phase separation (LLPS) was investigated for different polymers at various concentrations of drug and polymer. Solution nuclear magnetic resonance (NMR) spectroscopy revealed that polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVP-VA), and hypromellose (HPMC) distributed into the ibuprofen (IBP)-rich phase formed by LLPS when the amorphous solubility of IBP was exceeded. The amount of polymer in the drug-rich phase increased for higher-molecular-weight grades of PVP and HPMC. Moreover, PVP-VA showed a greater extent of distribution into the IBP-rich phase compared to PVP, and this is attributed to its reduced hydrophilicity resulting from the incorporation of vinyl acetate monomers. Direct quantification by NMR measurements indicated that the IBP concentration in the aqueous phase decreased as the amount of polymer in the IBP-rich phase increased. This can be attributed to a reduction of the chemical potential of IBP in the IBP-rich phase. The reduction in dissolved IBP concentration was greater for the IBP/PVP-VA system compared to the IBP/HPMC system, as a result of more extensive drug-polymer interactions in the former system. The present study highlights the impact of polymer selection on the attainable supersaturation of the drug and the factors that need to be considered in the formulation of ASDs to obtain optimized in vivo performance.

Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation.

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid-ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 µg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.

Dulaglutide-induced cerebral venous thrombosis in a patient with type 2 diabetes mellitus.

Though patients with diabetes mellitus are at a high risk of atherothrombotic events, every such event should not be attributed to the disease itself. We present a case of a patient with diabetes with headache and blurring of vision for 3 days. Brain imaging revealed right transverse sinus thrombosis and acute infarct of the right posterior parieto-occipital region, predominantly in the posterior cortical watershed zone. The patient was on subcutaneous dulaglutide for 3 weeks and was having nausea and vomiting. Various causes of cerebral venous thrombosis were ruled out with appropriate laboratory investigations. Finally, cerebral venous thrombosis was attributed to dulaglutide-induced nausea and vomiting which led to severe dehydration.

Diabetic ketoacidosis and thyroid storm: coexistence of a double trouble.

Diabetic ketoacidosis (DKA) and thyrotoxic crisis are both endocrine emergencies. Here, we present a case of a patient who presented with DKA and on further evaluation was found to also have a thyrotoxic crisis. The coexistence of both of these endocrine emergencies simultaneously is extremely rare and heralds grave prognosis unless identified and treated promptly.

The Effect of Daily versus Weekly Levothyroxine Replacement on Thyroid Function Test in Hypothyroid Patients at a Tertiary Care Centre in Haryana.

OBJECTIVE: We compare the effect of daily versus weekly levothyroxine (LT4) replacement on thyroid function test (TFT) in hypothyroid patients at a tertiary care centre in Haryana. MATERIALS AND METHODS: This was a randomised crossover study in which 100 hypothyroid patients on a stable LT4 dose were divided into 2 groups of 50 each. In group I, patients were given daily therapy for 6 weeks and then shifted to weekly therapy for the next 6 weeks. In group II, patients were given LT4 once a week for 6 weeks and then switched to daily therapy for the next 6 weeks. TFT, quality of life (QOL), and hyperthyroidism symptom scale (HSS) score of patients were compared in each group at 0, 6, and 12 weeks. RESULTS: TFT remained within the normal range, but TSH increased (group I, daily 2.8 ± 1.4 mIU/L, weekly 3.9 ± 1.1 mIU/L, p = 0.001; group II, weekly 4.6 ± 1.1 mIU/L, daily 2.7 ± 1.2 mIU/L, p = <0.001) and T3/T4 decreased with weekly therapy as compared to daily therapy. No significant difference in HSS score was found between daily and weekly administration of LT4. With weekly therapy, QOL showed improvement in bodily pain, vitality, mental health, and social functioning. CONCLUSION: Once-weekly LT4 administration is a reasonable alternative for patients, especially for those who have issues with compliance.

De La Chapelle Syndrome: A rare case of male infertility / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">A 25-year-old Indian male presented to Endocrine Outpatient Department of PGIMS Rohtak with chief complaints of inability to father a child in spite of 2 years of unprotected sexual intercourse. Patient had a normal male phenotype, however seminal fluid analysis was suggestive of azoospermia. Karyotyping chromosomal analysis showed 46, XX chromosomes. The frequency, etiology and diagnosis of this syndrome are reviewed here.</p>

Ringxiety and the Mobile Phone Usage Pattern among the Students of a Medical College in South India.

AIMS: Technologies like mobile phones may not always work positively but they may have unforeseen adverse effects. This study was conducted to find the proportion of students who experienced ringxiety (phantom ringing) and other perceived effects, as well as the pattern of the mobile phone usage among college students. METHOD: A cross-sectional study was carried out at Kasturba Medical College, Mangalore, south India, among 336 medical students by using a pre-tested, semi-structured questionnaire. RESULTS: Among the total number of students, 335 students possessed mobile phones. Mostly, the persons whom they talked to on their phones were parents for 220 (51%) of the students. 48% (150) talked for less than half hour in a day and 41% (137) were high volume message users. "Ringxiety" was experienced by 34.5% (116) of the students and they were more likely to use their phones at restricted places like classrooms (99%) and libraries (60.3%). A significantly larger proportion of ringxiety sufferers also complained of hampered studies. CONCLUSION: The pattern of mobile phone use among the medical students appeared to be problematic, as a fairly large proportion suffered from ringxiety, they reported getting very upset and they used their phones at restricted times and places. This problem needs to be recognized, all stakeholders must be made aware of the symptoms and measures must be taken to reduce it.