Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease.

OBJECTIVE: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia. DESIGN: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets. RESULTS: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage. CONCLUSIONS: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease.

Salvage Using Polatuzumab Vedotin Based Therapy in Relapsed Refractory Large B-Cell Lymphomas: Early Experience from a Real-World Middle-Income Setting Using Named-Patient Compassionate Access Program.

Polatuzumab vedotin is a novel immunotherapy antibody-drug conjugate targeting CD79b. It has been used in relapsed/refractory (R/R) large B-cell lymphomas since its FDA approval in 2019. Presently, this drug is unaffordable or unavailable for patients in Lower-Middle Income Countries (LMIC) like India. This is a retrospective study of adult (> 18 years) patients with R/R large B-cell lymphoma failing two prior lines of therapy, who received Polatuzumab based salvage therapy on a compassionate or named-patient access program. Between May 2019 and April 2022, 10 patients received Polatuzumab vedotin, and 9 were evaluable. The most common regimen used was Polatuzumab-Bendamustine-Rituximab. Out of 43 infusions administered, the adverse event profile was manageable [One grade-2 infusion reaction, 4 patients developed grade 3-4 hematological toxicity and none had grade 3-4 non-hematological toxicities]. Ten infusions were administered in the day care service. After a median of 4.5 cycles (range 1-8), 4 patients achieved CR, 2 had partial response (PR), and 3 had progressive disease (PD). With a median follow up of 491 days (range 8-1048 days), four patients are alive (three in CR and one in PR), three patients have died and three patients were lost to follow up. Early real-world experience from a LMIC setting demonstrates feasibility and a favourable safety profile of Polatuzumab vedotin based approach, along with encouraging response rates in a subset of patients.

Engineering new limits to magnetostriction through metastability in iron-gallium alloys.

Magnetostrictive materials transduce magnetic and mechanical energies and when combined with piezoelectric elements, evoke magnetoelectric transduction for high-sensitivity magnetic field sensors and energy-efficient beyond-CMOS technologies. The dearth of ductile, rare-earth-free materials with high magnetostrictive coefficients motivates the discovery of superior materials. Fe1-xGax alloys are amongst the highest performing rare-earth-free magnetostrictive materials; however, magnetostriction becomes sharply suppressed beyond x = 19% due to the formation of a parasitic ordered intermetallic phase. Here, we harness epitaxy to extend the stability of the BCC Fe1-xGax alloy to gallium compositions as high as x = 30% and in so doing dramatically boost the magnetostriction by as much as 10x relative to the bulk and 2x larger than canonical rare-earth based magnetostrictors. A Fe1-xGax - [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 (PMN-PT) composite magnetoelectric shows robust 90° electrical switching of magnetic anisotropy and a converse magnetoelectric coefficient of 2.0 × 10-5 s m-1. When optimally scaled, this high coefficient implies stable switching at ~80 aJ per bit.

Finite element analysis of patient-specific TMJ implants to replace bilateral joints with simultaneous correction of facial deformity.

INTRODUCTION: Finite element analysis (FEA) is a method to mimic the biomechanical behaviour of an object under various loading scenarios, and may be used during virtual planning of the TMJ prosthesis. Here we present an interesting case report where FEA was done to biomechanically evaluate patient specific total joint replacement prosthesis for bilateral TMJ replacement. CASE REPORT: A 22 year old young girl visited our outpatient clinic with a chief complaint of retruded chin and limited mouth opening for the last 15 years. After clinical and radiographic examination, her corrective surgery was virtually planned on Mimics software. The Implants were studied under simulated loading scenarios in ANSYS to understand the structural integrity of the implant for different loading conditions. RESULTS: Maximum Von-Mises Stress on Condylar component is 151.9 MPa and Maximum Von-Mises Stress on Fossa component is 0.377 MPa. The minimum safety factor of the fossa component was about 15, which is safe enough to complete 100 million cycles. The maximum von-mises stress were detected at the screw holes in the condylar components of the implant. The screw holes were therefore the areas prone to highest chance of failure in the design. CONCLUSION: We conclude that FEA based biomechanical analysis is important prerequisite during customized reconstruction of TMJ. In today's scenario of patient specific TMJ reconstruction, FEA based designing and planning of stress distribution along the bone and calculation of maximum strain in the prosthesis, further aids in the proper designing of this implant and enhances the post-operative clinical results.

Cystic echinococcosis in animals and humans of Maharashtra State, India.

Echinococcosis/hydatidosis which is a neglected parasitic zoonosis in the developing country like India. The study was conducted during April, 2010 to March, 2017 to determine the prevalence among slaughtered food animals, dogs and human. The samples were collected from the various slaughterhouses situated in different regions of Maharashtra state. A total of 9464 cattle (male), 3661 buffalo, 47189 sheep, 33350 goats and 13579 pigs were scientifically examined during PM inspection at different slaughterhouses. The study revealed that the prevalence of disease in cattle (3.00%) was highest followed by buffalo (2.05%), pig (1.28%), sheep (0.09%) and goat (0.01%), by PM examination. The average estimated economic losses (direct and indirect) due to hydatidosis were Rs. 8,65,83,566 in cattle, Rs. 44,33,93,900 in buffalo, Rs. 7,24,50,615 in sheep, Rs. 1,88,29,359 in goat and Rs. 5,20,49,081 in pigs. Dog faecal samples analyzed and showed the prevalence of echinococcosis as 4.34% (19/438) by sedimentation method and positive samples were confirmed by PCR assay, whereas in high risk human, 11.09% sera samples were found to be positive for echinococcosis. However, based on data collection for seven years, 58 patients were found to be surgically operated for hydatid cyst removal. The results of the present study indicated that cystic echinococcosis/hydatidosis is prevalent in both human and animal population in study areas which attracts serious attention from veterinary and public health authority to reduce economic burden and in designing appropriate strategy for prevention and control of disease.

Do Panic Symptoms Affect the Quality of Life and Add to the Disability in Patients with Bronchial Asthma?

Background. Anxiety and panic are known to be associated with bronchial asthma with variety of impact on clinical presentation, treatment outcome, comorbidities, quality of life, and functional disability in patients with asthma. This study aims to explore the pattern of panic symptoms, prevalence and severity of panic disorder (PD), quality of life, and disability in them. Methods. Sixty consecutive patients of bronchial asthma were interviewed using semistructured proforma, Panic and Agoraphobia scale, WHO Quality of life (QOL) BREF scale, and WHO disability schedule II (WHODAS II). Results. Though 60% of the participants had panic symptoms, only 46.7% had diagnosable panic attacks according to DSM IV TR diagnostic criteria and 33.3% had PD. Most common symptoms were "sensations of shortness of breath or smothering," "feeling of choking," and "fear of dying" found in 83.3% of the participants. 73.3% of the participants had poor quality of life which was most impaired in physical and environmental domains. 55% of the participants had disability score more than a mean (18.1). Conclusion. One-third of the participants had panic disorder with significant effect on physical and environmental domains of quality of life. Patients with more severe PD and bronchial asthma had more disability.

Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680.

UNLABELLED: A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead.

Shared or induced obsessive compulsive disorder: Is it a reality?

BACKGROUND: Shared or induced obsessive compulsive disorder (OCD) is not yet a distinct diagnosis in classification of psychiatric disorders. In fact, though recognized as a diagnostic category, shared or induced psychotic disorders are rare and most of the literature is based on the case reports. MATERIALS AND METHODS: We are reporting three case studies manifested with shared or induced OCD (cases with obsessive symptoms that were shared from the primary case in their family). RESULTS: All the cases were treated considering shared or induced OCD as psychopathology. Response to treatment modalities in first and second case and poor response to treatment in third case is suggestive of shared or induced OCD as a distinct entity. It is different from shared psychosis in many ways. CONCLUSION: Shared or induced OCD is a distinct diagnosis. Greater awareness about this entity among mental health professionals is needed.

Mechanical spin control of nitrogen-vacancy centers in diamond.

We demonstrate direct coupling between phonons and diamond nitrogen-vacancy (NV) center spins by driving spin transitions with mechanically generated harmonic strain at room temperature. The amplitude of the mechanically driven spin signal varies with the spatial periodicity of the stress standing wave within the diamond substrate, verifying that we drive NV center spins mechanically. These spin-phonon interactions could offer a route to quantum spin control of magnetically forbidden transitions, which would enhance NV-based quantum metrology, grant access to direct transitions between all of the spin-1 quantum states of the NV center, and provide a platform to study spin-phonon interactions at the level of a few interacting spins.

Isolation and characterization of halotolerant Streptomyces radiopugnans from Antarctica soil.

An actinomycete wild strain PM0626271 (= MTCC 5447), producing novel antibacterial compounds, was isolated from soil collected from Antarctica. The taxonomic status of the isolate was established by polyphasic approach. Scanning electron microscopy observations and the presence of LL-Diaminopimelic acid in the cell wall hydrolysate confirmed the genus Streptomyces. Analysis of 16S rRNA gene sequence showed highest sequence similarity to Streptomyces radiopugnans (99%). The phylogenetic tree constructed using near complete 16S rRNA gene sequences of the isolate and closely related strains revealed that although the isolate fell within the S. radiopugnans gene subclade, it was allocated a different branch in the phylogenetic tree, separating it from the majority of the radiopugnans strains. Similar to type strain, S. radiopugnans R97(T) , the Antarctica isolate displayed thermo tolerance as well as resistance to (60) Co gamma radiation, up to the dose of 15 kGy. However, media and salt tolerance studies revealed that, unlike the type strain, this isolate needed higher salinity for its growth. This is the first report of S. radiopugnans isolated from the Antarctica region. The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of Streptomyces radiopugnans MTCC 5447 is JQ723477.

Asymptomatic, isolated tubercular splenic abscess, in an immunocompetent person.

Tubercular splenic abscess in an immunocompetent person, especially when the patient is without any symptoms, is a rare clinical entity. We report a case of isolated tubercular splenic abscess in a 38-year-old asymptomatic healthy female and emphasize the importance of careful smear examination. The patient had come to the hospital for repair of vaginal vault prolapse. Her abdominal ultra sonography showed normal sized spleen with hypoechoic areas suggesting abscess. Fine needle aspiration of splenic lesion revealed tubercle bacilli on Ziehl Neelsen stain. The organisms also grew on culture. The splenic lesions cleared after six months of treatment with anti tubercular drugs at our Directly Observed Treatment centre under Revised National TB Control Programme. The patient was operated successfully for vault prolapse one year later.

Immunogenicity and safety of hepatitis B vaccine (Shanvac-B) using a novel pre-filled single use injection device Uniject in Indian subjects.

BACKGROUND: Hepatitis B is a major public health problem, which has now been controlled to some extent by vaccination especially with the recombinant hepatitis B vaccine, which has been proven to be safe and efficacious since its introduction in the 1990s. But problems of unsafe injection practices still persist. Now newer delivery devices like uniject are available for making vaccination very safe. OBJECTIVE: To evaluate the immunogenicity and safety of the Hepatitis-B (Shanvac-B) vaccine in Uniject pre-filled device administered to healthy adults and infants at 0, 1, 2 months schedule. METHODS: A total of 122 healthy subjects (62 adults and 60 infants) were administered three doses of the recombinant Hepatitis-B vaccine using Uniject pre-filled device. Blood samples for antibody titer estimation were taken before vaccination and 4-6 weeks after third dose. Subjects, parents or guardians were given diary cards to record any adverse reactions. RESULTS: Protective immune responses to the vaccine were seen in 96.4% of adults and 100% of infants who completed the study. The Geometric Mean Titers (GMT) in adults and infants were 518.5 and 385.41 mIU/ml respectively. Mild fever, itching, and swelling at injection site were the most common side effects observed. CONCLUSION: The safety and immunogenicity of the Hepatitis B Vaccine in the novel pre-filled device Uniject was effectively demonstrated in the present study.

Use of DNA markers in prediction of hybrid performance and heterosis for a three-line hybrid system in rice.

Two Cytoplasmic Male Sterile lines were crossed with fourteen restorer lines of rice widely grown in the western regions of Maharashtra, India, to produce 28 F1 hybrids which were evaluated for eight agronomically important traits, contributing to yield potential, in replicated field trials. The hybrid performance was recorded along with heterosis and heterobeltiosis. All the rice lines under investigation were subjected to marker-based variability analysis. An attempt was made to correlate genetic distance based on specific markers for each trait individually, as well as average genetic distance based on all specific markers, with hybrid performance and heterosis, by regression analysis. Specific markers could cluster the parental lines in different groups and showed significant correlation with hybrid performance. The data also supports the proposition that epistasis is the basis of heterosis. The analysis, however, revealed a lack of significant predictive values for field application.

Chronic ethanol exposure delays the 'developmental switch' of the NMDA receptor 2A and 2B subunits in cultured cerebellar granule neurons.

Chronic ethanol treatment of cultured neurons from various brain areas has been found to increase NMDA receptor function and to alter the levels of some NMDA receptor subunit proteins. Because the cultured neurons are exposed to ethanol during a period when the NMDA receptor is undergoing developmental changes in subunit expression, we wished to determine whether ethanol treatment alters this developmental pattern. We found that 3 days of treatment of cerebellar granule neurons with ethanol, which was previously reported to increase NMDA receptor function, resulted in a delay in the 'developmental switch' of the NR2A and NR2B subunits, i.e. the developmental decrease in NR2B and increase in NR2A protein expression. As a result, the level of NR2B was higher, and that of NR2A was lower, in the ethanol-treated cells than in control cells. Cross-linking experiments showed that the changes in total receptor subunit proteins levels were reflected in cell-surface expressed proteins, indicating changes in the amount of functional receptors. These results were confirmed by a higher potency of glycine at the NMDA receptor in the ethanol-treated cells, as determined by NMDA/glycine-induced increases in intracellular Ca(2+). The results suggest that the mechanism by which ethanol alters NMDA receptor expression in cultured neurons, where receptors are undergoing development, differs from the mechanism of ethanol's effect on NMDA receptors in adult brain. Changes in the proportion of NR2A and NR2B subunits may contribute to effects of ethanol on neuronal development.

Approach to recurrent respiratory infections.

Rational approach to diagnosis and management of recurrent respiratory infections is needed, or else the child is subjected to unnecessary investigations and multiple drugs. Repeated respiratory symptoms do not mean a respiratory infection. A diagnosis of viral infection does not justify prescription of an antibiotic. Recurrent viral infections are part of the growing up process of any child. Giving antibiotics at every episode to cover "so-called superadded bacterial infections" will lead to "recurrent antibiotics" and adverse effects on growth. Systematic approach should be used to find the underlying cause. An otoscopic examination of a child should form part of a pediatric examination in all cases of respiratory infections. Antibiotics should be judiciously chosen depending on age, socioeconomic status, severity of infection and the type of organism expected and always given in adequate doses and proper duration. Treatment should be specific and symptomatic. Adequate drainage of the sinuses is an important adjuvant therapy. Use of cough syrups with various combinations should be avoided. Efforts should be made to diagnose and treat manifestations of hyperactive airway or allergy, role of CEA (cough equivalent asthma) and WLRI (Wheeze associated lower respiratory infections). Investigations are needed in recent lower respiratory infections and adverse effect on growth, school performance, abnormal physical findings. CBC, CRP, ESR, nasal smear, appropriate cultures, tests for TB, X-Rays, barium studies, milk scan, ultra sound, CT, MRI, bronchoscopy in selected cases.

Chronic ethanol exposure attenuates the anti-apoptotic effect of NMDA in cerebellar granule neurons.

Ethanol, added to primary cultures of cerebellar granule neurons simultaneously with NMDA, was previously shown to inhibit the anti-apoptotic effect of NMDA. The in vitro anti-apoptotic effect of NMDA is believed to mimic in vivo protection against apoptosis afforded by innervation of developing cerebellar granule neurons by glutamatergic mossy fibers. Therefore, the results suggested that the presence of ethanol in the brain at a critical period of development would promote apoptosis. In the present studies, we examined the effect of chronic ethanol exposure on the anti-apoptotic action of NMDA in cerebellar granule neurons. The neurons were treated with ethanol in vitro for 1-3 days in the absence of NMDA. Even after ethanol was removed from the culture medium, as ascertained by gas chromatography, the protective effect of added NMDA was significantly attenuated. The decreased anti-apoptotic effect of NMDA was associated with a change in the properties of the NMDA receptor, as indicated by a decrease in ligand binding, decreased expression of NMDA receptor subunit proteins, and decreased functional responses including stimulation of increases in intracellular Ca(2+) and induction of brain-derived neurotrophic factor expression. The latter effect may directly underlie the attenuated protective effect of NMDA in these neurons. The results suggest that ethanol exposure during development can have long-lasting effects on neuronal survival. The change in the NMDA receptor caused by chronic ethanol treatment may contribute to the loss of cerebellar granule neurons that is observed in animals and humans exposed to ethanol during gestation.

Basic fibroblast growth factor inhibits cell proliferation in cultured avian inner ear sensory epithelia.

Postembryonic production of inner ear hair cells occurs after insult in nonmammalian vertebrates. Recent studies suggest that the fibroblast family of growth factors may play a role in stimulating cell proliferation in mature inner ear sensory epithelium. Effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) were tested on progenitor cell division in cultured auditory and vestibular sensory epithelia taken from posthatch chickens. The effects of heparin, a glycosaminoglycan that often potentiates the effects of the FGFs, were also assessed. Tritiated-thymidine autoradiographic techniques and 5-bromo-2;-deoxyuridine (BrdU) immunocytochemistry were used to identify cells synthesizing DNA. The terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end-label (TUNEL) method was used to identify apoptotic cells. TUNEL and overall counts of sensory epithelial cell density were used to assess possible cytotoxic effects of the growth factors. FGF-2 inhibited DNA synthesis in vestibular and auditory sensory epithelia and was not cytotoxic at the concentrations employed. FGF-1 did not significantly alter sensory epithelial cell proliferation. Heparin by itself inhibited DNA synthesis in the vestibular sensory epithelia and failed to potentiate the effects of FGF-1 or FGF-2. Heparin was not cytotoxic at the concentrations employed. Results presented here suggest that FGF-2 may be involved in inhibiting cell proliferation or stimulating precursor cell differentiation in avian inner ear sensory epithelia.