Population Pharmacokinetic Analyses for Tebipenem after Oral Administration of Pro-Drug Tebipenem Pivoxil Hydrobromide.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral (PO) carbapenem pro-drug that is converted to the active moiety tebipenem in the enterocytes. Tebipenem has activity against multidrug-resistant Gram-negative pathogens, including extended-spectrum beta lactamase-producing Enterobacterales, and is being developed for the treatment of patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). The objectives of these analyses were to develop a population pharmacokinetic (PK) model for tebipenem using data from three phase 1 studies and one phase 3 study and to identify covariates that described the variability in tebipenem PK. Following construction of the base model, a covariate analysis was conducted. The model was then qualified by performing a prediction-corrected visual predictive check and evaluated by using a sampling-importance-resampling procedure. The final population PK data set was composed of data from 746 subjects who provided 3,448 plasma concentrations, including 650 patients (1,985 concentrations) with cUTI/AP. The final population PK model that best described tebipenem PK was found to be a two-compartment model with linear, first-order elimination and two transit compartments to describe the rate of drug absorption after PO administration of TBP-PI-HBr. The relationship between renal clearance (CLR) and creatinine clearance (CLcr), the most clinically significant covariate, was described using a sigmoidal Hill-type function. No dose adjustments are warranted on the basis of age, body size, or sex as none of these covariates were associated with substantial differences in tebipenem exposure in patients with cUTI/AP. The resultant population PK model is expected to be appropriate for model-based simulations and assessment of pharmacokinetic-pharmacodynamic relationships for tebipenem.

Development of a novel one-step triplex PCR assay for the simultaneous detection of porcine circovirus type 2, porcine parvovirus and classical swine fever virus in a single tube.

Co-infection of multiple pathogens complicates diagnosis, treatment and preventive measures based on clinical signs. Therefore, reliable diagnostic tool for timely reporting of suspected diseases is very much essential. A novel one-step triplex PCR assay was developed and evaluated for simultaneous detection of three important viruses namely porcine circovirus type 2 (PCV2), porcine parvovirus (PPV) and classical swine fever virus (CSFV) involved in reproductive problems in pigs. Each of the three pairs of oligonucleotide primers exclusively amplified the targeted fragment of the specific viruses. The multiplex PCR assay was found to be sensitive in detecting at least 300 pg of viral genomic DNA or RNA from a mixture of three viruses in a reaction. No amplification was obtained from other common viruses or pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), Japanese encephalitis virus (JEV), porcine group A rotavirus (PoRVA), Escherichia coli and Staphylococcus aureus thereby indicating that the developed multiplex PCR has high specificity. Because of the sensitivity and specificity, the developed multiplex PCR assay will be a useful tool for clinical diagnosis of mixed infections of DNA and RNA viruses in pigs.

Butylated hydroxytoluene (bht) improves the post-thaw semen quality in low-dose sperm cryopreservation in murrah buffalo bull.

BACKGROUND: Cryopreservation is an important technique for the long-term storage of semen for artificial insemination (AI). Buffalo spermatozoa are sensitive to cryopreservation procedures because of the presence of a high amount of polyunsaturated fatty acids in the plasma membrane. OBJECTIVE: To study the effect of different concentrations of BHT on the quality of Murrah buffalo bull semen for low-dose cryopreservation. MATERIAL AND METHODS: Semen was collected from four high fertile Murrah buffalo bulls (6 ejaculates each) using an artificial vagina. A total of 24 ejaculates were collected from each bull twice a week using an artificial vagina. Every sample was split into four parts: Control without additives; and three treatments with BHT at 0.5 mM, 1 mM or 2 mM. Semen was cryopreserved at low-dose sperm cryopreservation of 20, 15, 10 and 5 million sperm per aliquot after supplementation of BHT. Semen samples were evaluated for fresh, pre-freeze and post-thaw stages. RESULTS: There was a significant increase (p<0.05) in sperm quality parameters, such as progressive motility (%), viability (%), HOST response (%), acrosome integrity (%) and post-thaw motility, with the addition of 0.5-1 mM BHT. CONCLUSION: The addition of BHT in Murrah buffalo semen improves the low dose cryopreservation quality in a dose-dependent manner. doi.org/10.54680/fr23110110612.

Reflectance based non-destructive determination of colour and ripeness of tomato fruits.

The preference and quality of tomato fruit are primarily determined by its apparent colour and appearance. Non-destructive and rapid methods for assessment of tomato colour and ripeness are therefore of immense significance. This study was conducted to identify reflectance-based indices and to develop models for the non-destructive determination of colour and ripeness (maturity) of tomato fruits. Tomato fruits of two varieties and two hybrids, representing different ripening stages were investigated. Fruits were either harvested directly from the plants or they were picked up from the lots stored at 25 °C. Reflectance from individual fruit was recorded in a spectrum ranging from 350 to 2500 nm. These fruits at different ripening stages were ranked on a relative ripening score (0.0-8.5). Obtained data (reflectance and ripening score) were subjected to chemometric analysis. In total, six models were developed. The first-best model was based on the index R521 (reflectance at wavelength 521 nm) i.e., y (colour/ripeness) = - 2.456 ln (x) - 1.093 where x is R521. This model had a root mean standard error of prediction (RMSEP) ≥ 0.86 and biasness = - 0.09. The second-best model y = 2.582 ln (x) - 0.805 was based on the index R546 (x) and had RMSEP ≥ 0.89 and biasness = 0.10. Models could bifurcate tomatoes into basic ripening stages and also red and beyond red tomato fruits from other stages across the varieties/hybrids and ripening conditions [for plant harvested (fresh) and stored (aged) fruits]. Findings will prove useful in developing simple and thereby cost-effective tools for rapid screening/sorting of tomato fruits based on their colour or ripeness not only for basic research (phenotyping) but also for the purpose of processing, value-addition, and pharmaceutical usages. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01126-2.

Impact of Early Blood Pressure Lowering in Patients Presenting with Acute Ischemic Stroke.

PURPOSE OF REVIEW: In this review article we will discuss the acute hypertensive response in the context of acute ischemic stroke and present the latest evidence-based concepts of the significance and management of the hemodynamic response in acute ischemic stroke. RECENT FINDINGS: Acute hypertensive response is considered a common hemodynamic physiologic response in the early setting of an acute ischemic stroke. The significance of the acute hypertensive response is not entirely well understood. However, in certain types of acute ischemic strokes, the systemic elevation of the blood pressure helps to maintain the collateral blood flow in the penumbral ischemic tissue. The magnitude of the elevation of the systemic blood pressure that contributes to the maintenance of the collateral flow is not well established. The overcorrection of this physiologic hemodynamic response before an effective vessel recanalization takes place can carry a negative impact in the final clinical outcome. The significance of the persistence of the acute hypertensive response after an effective vessel recanalization is poorly understood, and it may negatively affect the final outcome due to reperfusion injury. Acute hypertensive response is considered a common hemodynamic reaction of the cardiovascular system in the context of an acute ischemic stroke. The reaction is particularly common in acute brain embolic occlusion of large intracranial vessels. Its early management before, during, and immediately after arterial reperfusion has a repercussion in the final fate of the ischemic tissue and the clinical outcome.

Detection and localisation of hip fractures on anteroposterior radiographs with artificial intelligence: proof of concept.

AIM: To investigate the feasibility of applying a deep convolutional neural network (CNN) for detection/localisation of acute proximal femoral fractures (APFFs) on hip radiographs. MATERIALS AND METHODS: This study had institutional review board approval. Radiographs of 307 patients with APFFs and 310 normal patients were identified. A split ratio of 3/1/1 was used to create training, validation, and test datasets. To test the validity of the proposed model, a 20-fold cross-validation was performed. The anonymised images from the test cohort were shown to two groups of radiologists: musculoskeletal radiologists and diagnostic radiology residents. Each reader was asked to assess if there was a fracture and localise it if one was detected. The area under the receiver operator characteristics curve (AUC), sensitivity, and specificity were calculated for the CNN and readers. RESULTS: The mean AUC was 0.9944 with a standard deviation of 0.0036. Mean sensitivity and specificity for fracture detection was 97.1% (81.5/84) and 96.7% (118/122), respectively. There was good concordance with saliency maps for lesion identification, but sensitivity was lower for characterising location (subcapital/transcervical, 84.1%; basicervical/intertrochanteric, 77%; subtrochanteric, 20%). Musculoskeletal radiologists showed a sensitivity and specificity for fracture detection of 100% and 100% respectively, while residents showed 100% and 96.8%, respectively. For fracture localisation, the performance decreased slightly for human readers. CONCLUSION: The proposed CNN algorithm showed high accuracy for detection of APFFs, but the performance was lower for fracture localisation. Overall performance of the CNN was lower than that of radiologists, especially in localizing fracture location.

Incubation with Cholesterol-loaded Cyclodextrin and Subsequent Dilution in Partially Deoxygenated Extender Improves the Freezability of Cross-bred Bull Sperm.

BACKGROUND: The cryopreservation process induces osmotic stress, membrane changes and production of reactive oxygen species resulting in damage to the spermatozoa. Together, the presence of oxygen in the extender aggravates the oxidative stress that further reduces the cryosurvival rate of sperm cells. OBJECTIVE: To study the combined effect of cholesterol loaded cyclodextrin (CLC) and partial deoxygenation on post-thaw semen quality in crossbred bulls. MATERIALS AND METHODS: A total of 18 ejaculates from three crossbred bulls with >3+ mass motility and >70% individual progressive motility were utilized for the study. Each semen sample was divided into four groups: Group I (containing extender without partial deoxygenation or CLC addition); Group II (extender containing 3 mg CLC/120X106 spermatozoa); Group III (extender containing 3 mg CLC/120X106 spermatozoa and 4 ppm dissolved oxygen (DO) level); Group IV (extender containing 3 mg CLC/120X106 spermatozoa and 6 ppm DO level). The samples in each group were finally extended to have 80×106 progressive motile sperm/mL of extender, filled and sealed in French mini straws (0.25 mL) and frozen following equilibration. The effect of CLC addition and partial deoxygenation was assessed at fresh (post-dilution), pre-freeze and post-thaw stages by evaluating various variables [sperm motility, viability, hypo-osmotic swelling (HOS) response, acrosomal integrity, capacitation status and mitochondrial membrane potential (MMP)]. RESULTS: The sperm population was significantly more positive for motility, viability, HOS response, acrosome intactness, high MMP and had less capacitation-like changes in groups supplemented with CLC and partially deoxygenation. However, the positive effect was most pronounced in the group that had extender with CLC+4 ppm DO. CONCLUSION: Partial deoxygenation of extender, and CLC addition in combination, could be part of a rationale for improving post-thaw semen quality in cross-bred bulls.

Alterations of hemogram, serum biochemistry, oxidative/nitrosative balance, and copper/zinc homeostasis in dromedary camels naturally infected with poxvirus.

Camel pox (CMLP), a contagious viral disease of camels, causes considerable economic loss in terms of milk, meat, wool, and leather production besides reduction of draught power. The effect of spontaneous CMLP infection on hemogram, oxidative/nitrosative imbalance, and trace mineral homeostasis has not been studied earlier in dromedary camels. In the current study, hemogram, serum biochemistry, oxidant/antioxidant imbalance, and zinc (Zn)-copper (Cu) homeostasis were evaluated in healthy and pox-infected camels. The CMLP was confirmed from pooled samples of vesicular fluid, oral mucosa, and skin samples by polymerase chain reaction (PCR) targeting the C18L gene of CMLP virus. Hemogram was performed manually in whole blood. The serum was analyzed for biochemistry. The oxidative/nitrosative imbalance was measured by determining the concentrations of malondialdehyde (MDA), nitrite and nitrate (NOx), and glutathione S-transferase (GST) activity in serum. Simultaneously, copper (Cu) and zinc (Zn) concentrations were measured in serum. A pronounced leucopenia (p = 0.019), lymphopenia (p = 0.005), and hypoproteinemia (p = 0.014) were noted in CMLP-infected camels compared to healthy animals. The significant elevation of the MDA (p = 0.005) and NOx (p = 0.044) concentrations in serum of CMLP-infected indicated marked oxidative stress during the disease. The zinc concentration (p = 0.014) in CMLP-infected camels was significantly lower than healthy camels. The study supports that oxidative/nitrosative imbalance and Cu-Zn homeostasis are compromised and related to the pathophysiology of CMLP infection. The finding will be helpful to veterinary clinicians to adopt effective therapeutic strategies using antioxidants and trace minerals during CMLP outbreak. The timely vaccination and bio-security will be the mainstay for prevention of the diseases.

Was Hawan Designed to Fight Anxiety-Scientific Evidences?

Anxiety is a psychiatric disorder with unknown neurobiology; however, neurotransmitters like gamma-amino butyric acid, norepinephrine and serotonin (5-HT) play crucial roles in mediating anxiety. Present drug modules pose dependence risk to the patient; hence, there is a great need to develop complementary therapies to fight this disorder. Aromatherapy has also been employed in ancient times for a number of mental disorders. Mahamrituanjay Mantra, Om triambkum yajamahe, sughandhim puushtivardhanam, urvarukmev vandhanaat, mrityu mokshay mamritaat!!!!, the part of veda enlightens that aroma gives rise to good health (sughandhim puushtivardhanam). Hawan is a religious practice recommended for mental peace. Hawan is a process in which special herbs are offered in the fire of medicinal woods ignited in a specially designed fire pit. Analysis of literature demonstrates that the components of Hawan are having a number of volatile oils that are specifically useful for prevention and treatment of anxiety through some mechanism of action. Due to high temperature of fire, the vapors of these oils from herbs enter into the central nervous system through nasal route. As per modern science and ancient texts on medicine, nasal drug delivery systems are the best for the diseases related to brain and head. The routine of performing Hawan might keep the threshold value of the therapeutic components in the body and help in preventing anxiety. In the present manuscript, authors highlight and integrate the modern and ancient concepts for treatment and prevention of anxiety through scientific evidences.

Travel time to health facilities in areas of outbreak potential: maps for guiding local preparedness and response.

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.

What do Vitiligo Impact Scale-22 scores mean? Studying the clinical interpretation of scores using an anchor-based approach.

BACKGROUND: The Vitiligo Impact Scale (VIS)-22 is a vitiligo-specific quality-of-life instrument. Its criterion, convergent and known-groups validity, test-retest reliability and responsiveness have been studied previously in an Indian population. The clinical meaning of VIS-22 scores has not yet been analysed. OBJECTIVES: To assign clinical meaning to VIS-22 scores using anchor-based methods. METHODS: This was a cross-sectional study conducted in a large teaching hospital in North India. Patients with vitiligo > 15 years of age (n = 391) completed the VIS-22 and Dermatology Life Quality Index (DLQI) questionnaires, and answered a Global Question (GQ) on the effect of vitiligo on their lives on a five-point Likert scale. Multiple band sets of VIS-22 scores were devised using GQ as the anchor. A weighted kappa-coefficient was calculated to estimate the level of agreement between different band sets of VIS-22 and GQ. VIS-22 and DLQI were compared based on their degree of correlation and agreement with GQ. RESULTS: The mean ± SD of VIS-22 scores was 24·8 ± 14·0 (range 0-61). VIS-22 scores showed good correlation with GQ (r = 0·76). Of the various VIS-22 band sets tested, the following was chosen: 0-5, 6-15, 16-25, 26-40 and 41-66 (weighted κ = 0·57), corresponding to the five categories of GQ. The degree of correlation (VIS-22, r = 0·77; DLQI, r = 0·69) and agreement (VIS-22, 51·6%; DLQI, 36·1%; P < 0·001) of VIS-22 with GQ was higher than that with DLQI. CONCLUSIONS: VIS-22 scores can be used to stratify the impairment of vitiligo-related quality of life.

Elemental impurities in pharmaceutical products adding fuel to the fire.

The pharmaceuticals may generate impurities at various stages of development, transportation and storage which make them risky to be administered. Thus, it is essential that these impurities must be detected and quantified. However, their presence as impurities in finished products is virtually unavoidable, even under GMP conditions. Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled due to lack of publicly available information on elemental impurity levels in common pharmaceutical excipients. The present compilation gives an account of updated information about elemental impurities and reviews the regulatory aspects for such impurities in active pharmaceutical ingredients/drug formulations. In addition, the aim of this article is to review and discuss the currently used quantitative analytical method, which is used for quality control of elemental impurities in pharmaceutical products.

Haptoglobin and serum amyloid A as putative biomarker candidates of naturally occurring bovine respiratory disease in dairy calves.

Bovine respiratory disease (BRD) is one of the leading causes of morbidity and mortality in dairy calves. Identification of reliable biomarkers of naturally occurring BRD is essential for ensuring early diagnosis and treatment of calves and monitoring treatment efficacy. This need is punctuated, especially in mild to moderate cases that would greatly help to decrease recurrence and the overall prevalence of BRD. The present study was conducted to investigate the changes in serum concentrations of haptoglobin (Hpt) and serum amyloid A (SAA) and association between oxidative stress and acute phase proteins (APPs) in BRD. Hpt and SAA levels significantly increased (P < .01) in BRD stressed calves as compared to healthy subjects. There was a significant decrease (P < .01) in serum albumin (Alb) concentration of infected calves as compared to controls. The oxidative stress markers revealed a significant (P < .01) increase in lipid peroxidation (LPO) and a concurrent decrease in activities of superoxide dismutase (SOD), reduced glutathione (R-GSH) and catalase (CAT) in BRD. A significant correlation among APPs, extent of oxidative stress and clinical score (CS) of calves was depicted. A stepwise decrease in Hpt and SAA and increase in Alb was observed in infected calves post-treatment. These results suggest implication of oxidative stress in enhancing APPs and monitoring of APPs as a potential complement to clinical assessment of treatment in calves with naturally occurring BRD. Hpt may be useful as the most sensitive biomarker in BRD. However, the combined use of Hpt and oxidative stress biomarkers would greatly improve the diagnostic accuracy.

Association of ITGAM, TNFSF4, TNFAIP3 and STAT4 gene polymorphisms with risk of systemic lupus erythematosus in a North Indian population.

Several susceptibility genes have been associated with systemic lupus erythematosus (SLE) across different populations worldwide. However, data on association between genetic polymorphisms and SLE from Indian population is scarce. We aimed to replicate the association of single nucleotide polymorphisms (SNPs) in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes with susceptibility to SLE in a North Indian population. Three hundred and ninety-four SLE patients and 583 unrelated healthy controls of the same ethnic background were enrolled. All samples were genotyped for SNPs in ITGAM (rs1143679), TNFSF4 (rs2205960), TNFAIP3 (rs5029939) and STAT4 (rs7574865) using TaqMan genotyping assay. At allele level, significant association with susceptibility to SLE was detected with polymorphisms in ITGAM (A vs. G, odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.30-2.30, p < 0.001), TNFSF4 (T vs. G, OR = 1.33, 95% CI = 1.08-1.64, p < 0.01), TNFAIP3 (G vs. C, OR = 1.91, 95% CI = 1.27-2.85, p < 0.01) and STAT4 (T vs. G, OR = 1.38, 95% CI = 1.13-1.69, p < 0.01). All four SNPs were associated with SLE under a dominant model with an OR of 1.47 (95% CI = 1.07-2.04, p < 0.05) for ITGAM, 1.30 (95% CI = 1.01-1.69, p < 0.05) for TNFSF4, 1.90 (95% CI = 1.25-2.90, p < 0.01) for TNFAIP3 and 1.38 (95% CI = 1.06-1.78, p < 0.05) for STAT4. Under a recessive model, significant association was found with ITGAM (OR = 4.87, 95% CI = 2.17-10.91, p < 0.001), TNFSF4 (OR = 1.84, 95% CI = 1.13-3.00, p < 0.05) and STAT4 (OR = 1.82, 95% CI = 1.19-2.77, p < 0.01). In conclusion, single nucleotide polymorphisms in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes are associated with susceptibility to SLE in a North Indian population.

Development and evaluation of a gold nanoparticle-based immunochromatographic strip test for the detection of canine parvovirus.

Canine parvovirus (CPV) is the leading viral cause of enteritis in dogs and occurs mainly in 6- to 8-week-old pups. Rapid diagnosis of CPV under field conditions is now possible due to commercially available immunochromatographic (IC) assays. However, these commercial kits are somewhat expensive because they utilize a minimum of two monoclonal antibodies (mAbs) targeting different epitopes as capture and detector antibodies. Using only a single mAb for both capture and detection purpose may reduce the sensitivity of the assay. In the present study, efforts were made to develop an economical assay that can be utilized for diagnosis of CPV under Indian conditions with a high level of confidence. Rabbit polyclonal antibodies (pAbs) generated against recombinant truncated VP2 proteins of CPV were used as capture antibodies because they can be produced economically, while a commercial anti-CPV mAb was used as the detector antibody. The detection limit of the test strip was 6.6×105 TCID50/ml, and it specifically detected CPV-2, CPV-2a and CPV-2b while displaying no cross-reactivity with other common canine enteric pathogens. The relative sensitivity/specificity of pAb based strip test was 71%/92% and 71%/100% in relation to the hemagglutination test and a commercial IC kit, respectively, with substantial agreement. In addition, two commercially available mAbs targeting different epitopes were also used for development of another IC assay, which showed sensitivity, and specificity of 82%/87% and 90%/98% in relation to the hemagglutination test and commercial kit. Hence, the present strip test based on a combination of mAb and pAb provides an acceptable alternative for onsite and cost-effective diagnosis of CPV infection.

Rapid visual isothermal nucleic acid-based detection assay of Brucella species by polymerase spiral reaction.

AIM: The aim of this study was to develop polymerase spiral reaction (PSR) for rapid, sensitive and specific detection of Brucella sp. METHODS AND RESULTS: Polymerase spiral reaction assay was developed using specifically designed primers targeting the conserved multicopy IS711 gene of Brucella sp. The assay could be performed within 60 min at an isothermal temperature of 64°C. The lower limit of detection of PSR was 11·8 fg and conventional PCR was 1·18 pg of Brucella abortus genomic DNA. Thus, PSR was found to be 100-fold more sensitive than conventional PCR and was comparable to real-time PCR. The specificity of PSR was tested with other non-Brucella bacteria and also with some bacterial and viral pathogens causing abortions. The assay was found to be specific as it did not detect any putative pathogens other than Brucella sp. Fifty-six clinical samples suspected for brucellosis (aborted fetal stomach content) were screened with PSR to validate the applicability of the test to detect Brucella DNA. The same samples were also screened with conventional PCR and real-time PCR. Of 56 samples, 25 samples were found to be positive with both PSR as well as real-time PCR, whereas only 20 samples were found positive with conventional PCR. CONCLUSIONS: The results of this study indicated that the PSR assay is a simple, rapid, sensitive and specific method for the detection of Brucella sp. that may improve diagnostic potential in clinical laboratories or can be used at diagnostic laboratories with minimal infrastructure. SIGNIFICANCE AND IMPACT OF THE STUDY: The PSR assay, because of its simplicity and low cost, can be preferred to other molecular methods in the diagnosis of infectious diseases.

Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry.

BACKGROUND: The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively. AIMS: To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry METHODS: Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer. RESULTS: The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61-0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64-0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I-III and IV, and ≥ 47 between IV and V-VI. CONCLUSIONS: Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

Chronic nonbacterial osteomyelitis from a tertiary care referral center.

Chronic nonbacterial osteomyelitis (CNO) is a little known autoinflammatory bone disorder primarily affecting children and sometimes young adults. Diagnosis is often delayed due to its varied and nonspecific initial symptoms. Very few cases are reported from India. The aim of this report is to increase the awareness of this disease among physicians, orthopedic surgeons, and rheumatologists. Four male patients were diagnosed with CNO in the past 3 years. The age at onset varied from 9 to 23 years with a median diagnostic delay of 3.5 years. All patients presented with recurrent bony pain with or without localized swelling over the affected bones. Two patients had previously undergone open surgical procedures with bone biopsies and three patients had received at least one course of antibiotics. Two patients responded well to nonsteroidal anti-inflammatory drugs alone, one patient required a short course of glucocorticoids, and another patient required methotrexate to control disease activity. This case series includes males, onset at a relatively later age in most, and a longer diagnostic delay. Thus, in addition to children and adolescents, CNO should be suspected in young adults presenting with recurrent bony pain with or without localized swelling.

The inheritance of juvenile onset primary open angle glaucoma.

Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.

Costs and benefits of sublethal Drosophila C virus infection.

Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed several immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes, we find that even apparently benign, sublethal infections with the horizontally transmitted Drosophila C virus (DCV) can cause significant physiological and behavioural morbidity that is relevant for host fitness. We describe DCV-induced effects on fly reproductive output, digestive health and locomotor activity, and we find that viral morbidity varies according to the concentration of pathogen inoculum, host genetic background and sex. Notably, sublethal DCV infection resulted in a significant increase in fly reproduction, but this effect depended on host genotype. We discuss the relevance of sublethal morbidity for Drosophila ecology and evolution, and more broadly, we remark on the implications of deleterious and beneficial infections for the evolution of insect immunity.