Enabling ultra-low-voltage switching in BaTiO3.

Single crystals of BaTiO3 exhibit small switching fields and energies, but thin-film performance is considerably worse, thus precluding their use in next-generation devices. Here, we demonstrate high-quality BaTiO3 thin films with nearly bulk-like properties. Thickness scaling provides access to the coercive voltages (<100 mV) and fields (<10 kV cm-1) required for future applications and results in a switching energy of <2 J cm-3 (corresponding to <2 aJ per bit in a 10 × 10 × 10 nm3 device). While reduction in film thickness reduces coercive voltage, it does so at the expense of remanent polarization. Depolarization fields impact polar state stability in thicker films but fortunately suppress the coercive field, thus driving a deviation from Janovec-Kay-Dunn scaling and enabling a constant coercive field for films <150 nm in thickness. Switching studies reveal fast speeds (switching times of ~2 ns for 25-nm-thick films with 5-µm-diameter capacitors) and a pathway to subnanosecond switching. Finally, integration of BaTiO3 thin films onto silicon substrates is shown. We also discuss what remains to be demonstrated to enable the use of these materials for next-generation devices.

Association of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma species infection and organism load with cervicitis in north Indian population.

Cervicitis is predominantly caused by Neisseria gonorrhoeae and Chlamydia trachomatis, which accounts for almost half of all the cases of cervicitis. The role of newer organisms like Mycoplasma genitalium and Ureaplasma sp. and association of bacterial load with cervicitis are also not well established. So the study aimed to determine the relative frequency of these organisms and their load in association with cervicitis cases from north India. A case-control study involving 300 women was conducted using quantitative real-time PCR from endocervical swabs for identification of organisms and quantification of bacterial load. Among 150 cervicitis cases, C. trachomatis, N. gonorrhoeae, M. genitalium and Ureaplasma parvum were detected in 5 (3·3%), 10 (6·6%), 37(24·6%) and 47 (31·3%) respectively. Old age (<0·001, chi-squared test) and irregular menstrual cycles (<0·001, chi-squared test) were significantly associated with cervicitis. M genitalium was the only organism to be associated significantly with cervicitis with regard to age (<0·031) and symptoms like discharge (P < 0·033, chi-squared test) and dysuria (P < 0·044, chi-squared test) in multivariate analysis. Our finding suggests that the bacterial load of these organisms is not significantly associated with cervicitis. However, we found significant association of M. genitalium infection with clinical characteristics of cervicitis cases.

Predictive mechanistic model for single-layered pressure-sensitive adhesive (PSA) joints : Part I: Uniaxial tensile stress-strain response.

Modeling the deformation of structures containing pressure-sensitive adhesive (PSA) joints can be a challenging task because of the dependence of the deformation mechanism on a) PSA adhesive properties and b) the bonding substrate's surface properties, such as surface energy and surface roughness. These parameters have significant and unique effects on the mechanical response of the joint. This paper is part of a two-part series, where a mechanism-based predictive modeling approach, supported by empirical observations, is presented for modeling the uniaxial tensile mechanical behavior of single-layered PSA joints based on acrylic PSA materials. This paper (Part I) addresses the stress-strain response, while Part II of this series will address the creep behavior. The underlying model is based on multiple mechanisms: i) cavity nucleation and growth in the bulk adhesive material of the PSA system, as well as at the interfaces between the PSA and the substrate; ii) fibrillation of the cavitated adhesive layer and iii) interfacial slippage between the adhesive and the bonding substrate; iv) PSA delamination from the substrate. This predictive model can be used as a virtual testing tool to generate stress-strain curves for constitutive models of PSA joints under different tensile loading conditions.

Association of Serum Vitamin D Level with its Receptor Gene Polymorphism BSML in Beta Thalassemia Major Patients from East India.

Background Vitamin D deficiency is commonly identified in beta thalassemia major patients, related to iron accumulation.Vitamin D mediates its action upon binding to vitamin D receptor (VDR), a classical nuclear receptor. Several single nucleotide gene polymorphisms has been identified in VDR gene among which Bsml is commonly studied for its association with bone mineralisation and osteoporosis. Objective To explore the association between the Vitamin D Receptor Polymorphism (BsmI) and serum levels of Vitamin D, ionised Calcium, alkaline phosphatase in patients with beta thalassemia major. Method VDR gene was studied for Bsml polymorphisms from purified DNA in thirty six beta thalassemic patients (cases) - fourteen male and twenty two females, and thirty three controls after amplification by PCR followed by restriction digestion using appropriate restriction enzymes. Allelic differences between two groups were assessed by chi square and odds ratio test. Any potential link between the polymorphic variations and vitamin D status were assessed by post hoc ANOVA with bonferroni correction among the three genotypes. Result The distribution of BB genotype was significantly higher among the case groups (thalassemic group, χ2 = 9.77, p= 0.008). The odds ratio for the allele B was significantly higher in thalassemia group for a range of 1.97 to 5.94 for 95 percent cofidence interval (χ2 =10.4, p=0.0013). Serum Vitamin D, ionised Calcium were significantly low (p < 0.001) and Alkaline phosphatase (p < 0.001), was significantly high in thalassemics (cases). The genotype BB group had significantly low Vitamin D (p=0.001) and ionised Calcium (p < .001) compared to Bb and bb. The bb genotype had the highest levels of Vitamin D and ionised Calcium among the three genotypes. Conclusion The thalassemic patients are prone to Vitamin D deficiency and the superimposed predominance of BB genotype in them may be a risk factor for osteoporosis and cardiac dysfunction. Moreover, the study indicated genotype bb to have a probable protective role against Vitamin D deficiency in beta thalassemic patients.

Assessment of Variations in Oxidative Stress in Newborns from Caesarian and Normal Delivery Based on Apgar Score.

Fetal distress seems to be strongly related to fetal hypoxia, which is known to cause derangement of the balance between pro-oxidant and anti-oxidant factors by depleting the antioxidant reserve and increasing oxidative stress. Reduced Apgar score signify the fetal distress in postpartum period. The current study explores the severity of oxidative stress and nitrosative stress markers along with the antioxidant status in the cord blood of the newborns with low Apgar score (Group 1), fairly low Apgar score (Group 2) and normal Apgar score (Group 3) in both categories born by Cesarean section (CS) and Normal delivery (ND). Cord blood was collected from eighty full terms, mature neonates of both sexes; forty born via ND and 40 delivered by CS. Apgar scores were recorded and they were grouped based on the different levels of the score. Methemoglobin (HbM), RBC glucose-6-phosphate dehydrogenase (G6PD), RBC reduced glutathione (GSH) were measured as markers of oxidative stress, whereas serum nitrate and nitrite levels were assayed as markers of nitrosative stress. The data obtained were analyzed for the level of significance between study variables. One way ANOVA revealed statistically significant difference between the means of HbM (1.48±0.52, 1.03±0.4 and 0.69±0.31 for Group 1, 2 and 3 respectively, p<0.001), RBC G6PD (15.62±1.99, 18.16±2.47, 21.93±3.91) RBC GSH (7.7±1.55, 10.75±2.31, 16±6.10), serum nitrate (63.18±17.14, 49.29±14.39, 40.86±8.83) serum nitrite (4.89±1.8, 4.64±1.04, 3.69±0.72) between the three groups of ND neonates. The results were almost similar in CS neonates (HbM - 2.17±0.95, 1.45±0.62, 0.8±0.3; G6PD - 12.54±2.31, 14.31±2.17, 18.1±3.13; GSH - 7.6±2.23, 9±2.11, 12.78±2.83) except serum nitrate and nitrite where no significant difference was found between means among the different Apgar groups. The results suggest that lowest Apgar score ND neonates are exposed to highest oxidative, nitrosative stress and have the poorest antioxidant defense. The CS neonates have the similar fate except the insignificant difference between the nitrosative stresses among the three Apgar score groups signifying that they are better protected against the nitrosative stress than their ND counterparts.

Work Related Musculoskeletal Morbidity among Tailors: A Cross Sectional Study in a Slum of Kolkata.

Background Musculoskeletal disorders comprise the single largest group of work-related illnesses in developing countries. Sedentary working style with wrong posture for long time is considered to be an important risk factor, which is largely modifiable. Objective This study was performed to determine the prevalence and find out the factors associated with Musculoskeletal disorders among the workers involved in tailoring occupation. Method A descriptive community based cross-sectional study was conducted in the urban slums of Chetla, Kolkata on March and April, 2015. One hundred and ten (110) out of 383 resident tailors in the area were chosen by simple random sampling and interviewed by approaching them in their work place. Descriptive statistics and multivariable logistic regression were used Result Using Nordic Musculoskeletal questionnaire, Musculoskeletal disorders was found among 65.45% of tailors. The most commonly affected site was neck (41.8%) followed by lower and upper back. In bivariate analysis, musculo-skeletal disorders was found to be significantly associated with age more than 45 years [OR (95% CI)= 3.35 (1.30- 8.60)], working for > 10 years [OR (95% CI)= 7.01 (2.93-16.79)*], working > 8 hours per day [OR (95% CI)= 2.75 (1.20-6.20)], full time job [OR (95% CI)= 2.41 (1.08-5.39)] and unfavourable workstation ergonomic [OR (95% CI)= 2.40 (1.10-5.40)], whereas in multivariate analysis age, sex, duration in the profession [AOR (95%CI= 4.40 (1.40- 14.30)], working hours per day [AOR (95%CI= 7.20 (1.80-27.80)], and unfavourable workstation ergonomic [AOR (95%CI)= 3.50 (1.26-9.80)] remained significant. Conclusion A multidimensional approach including appropriate technique in terms of operators' posture and ergonomically sound workstation are required to avoid the debilitating effect of Musculoskeletal disorders among the workers.

Effect of Sub Clinical Hypothyroidism on C-reactive Protein and Ischemia Modified Albumin.

Thyroid disorders are associated with imbalance in redox status throughout the body along with a pro-inflammatory state. Aim of our present study was to evaluate any potential role of ischemia modified albumin (IMA) in both sub clinical and established hypothyroidism and to explore its potential relationship with the hsCRP. Serum TSH, fT4, IMA and hsCRP were measured in 30 cases and 40 age and sex matched controls by ELISA and standard photometric techniques. IMA value was compared between the sub clinical and clinical hypothyroid patients. Strength of association between the IMA and hsCRP was assessed also to analyze the prevalence of pro-inflammatory condition in hypothyroid patients. Serum values (mean ± SD) of hsCRP (07.49 ± 2.73), TSH (22.18 ± 12.9) and IMA (128.31 ± 16.96) were significantly higher in the case group. Bivariate correlation study indicated that TSH and fT4 showed direct and inverse relationship respectively with the hsCRP and IMA. IMA itself exhibited direct correlation with the pro-inflammatory marker hsCRP showing a positive correlation with IMA. Results of the general linear model analysis showed that only TSH had a significant positive predictive value on IMA while fT4 itself as a continuous covariate, or in the fraction of its normal or subnormal range, did not show any significant predictive value on IMA values. We suggest in conclusion that a pro-inflammatory status and derangement of the redox balance towards an overall ischemic state start at an early stage of sub clinical hypothyroidism. Early detection of these parameters may help in provision of necessary preventive measures against complications of hypothyroidism.

Association between Vitamin D Receptor Gene Polymorphism (Fok 1), Vitamin D Status and Autoimmune Thyroiditis.

Autoimmune thyroiditis gradually destroys the thyroid gland leading to hypothyroidism and may even lead to papillary thyroid carcinoma. Deficiency of Vitamin D has been linked to development of autoimmunity. Single nucleotide polymorphisms of the Vitamin D receptor gene have associated with autoimmune diseases in several studies. In this hospital based non interventional cross-sectional study Vitamin D receptor gene was studied for FokI (rs2228570) polymorphism from purified DNA in forty-eight adult cases and fifty age and sex matched healthy controls. This study was conducted in the department of Biochemistry, Calcutta National Medical College, Kolkata, West Bengal, India from January 2021 to July 2022. Their DNA was isolated using phenol chloroform method and were analysed for the related single nucleotide polymorphism by restriction digestion using appropriate restriction enzymes after amplification by PCR. Differences in allele frequencies between two groups were estimated by chi square and odds ratio test. Any potential association between the vitamin D anti TPO antibody and thyroid hormone status with polymorphic variations were assessed by post hoc ANOVA among the three genotypes. The distribution of FF genotype was significantly higher among the case group (Χ²=10.2788, p=0.006). The odds ratio for the allele F was significantly higher in case group for a range of 1.97 to 5.94 for 95 percent confidence interval (Χ²=13.9678, p=<0.001). The genotype FF group had significantly lowest Vitamin D (p=0.008) and highest Anti TPO ab (p=0.031) compared to Ff and ff genotypes. Thus, significant association was revealed between the VDR gene Fok1(rs2228570) polymorphism and autoimmune thyroiditis with the predominance of FF genotype being a strong susceptibility factor for autoimmune thyroiditis and Vitamin D deficiency in the studied population of Eastern India.

A Single-Institution Review of the Use of Radiation in the Adjuvant and Definitive Management of Keloids.

AIMS: Many individuals suffer from keloids that are refractory to standard treatment modalities, including surgical excision alone. Radiation therapy can be used to reduce the risk of recurrent keloids post-operatively, as well as be used as primary treatment for keloids not amenable to surgical resection. The purpose of this study was to review our institutional experience of radiation therapy for keloid management. MATERIALS AND METHODS: A retrospective review of patients treated with radiation therapy for keloids between 2014 and 2020 at our institution was performed. RESULTS: A total of 70 keloids in 41 patients were treated. For the 55 keloids treated with post-operative radiation therapy (16Gy delivered in 2 fractions), 82.5% (33/40) of evaluable lesions did not recur. Among the 15 keloids treated with definitive radiation therapy (24Gy delivered in 3 fractions), 78.6% (11/14) of evaluable keloids showed complete flattening, and 14.3% (2/14) had partial flattening. Both acute and late toxicities were mild, with only a single instance of grade 3 toxicity (dermatitis). CONCLUSION: Our study confirms that radiation therapy has a role in reducing the risk of keloid recurrence post-operatively, and plays an important role in the definitive management of unresectable keloids.

Serum uric acid: an early indicator of oxidative stress in beta thalassemia population.

Iron induced alteration in the redox balance is a major complication in the beta thalassemia major patients receiving regular blood transfusion. Variable degrees of association between uric acid level with the free iron and its storage form ferritin in thalassemic patients are suggested to play a significant role in this alteration by an unclear mechanism. In the present study, we made an effort to analyze the association of serum uric acid with oxidative stress and to evaluate the predictive value of serum iron, serum ferritin and serum uric acid level on oxidative stress induced lipid peroxidation in beta thalassemic patients. For this we assayed these parameters in 61 patients of ß thalassemia major and 51 age and sex matched controls of a rural area of West Bengal. Serum TBARS, serum Uric acid, serum Ferritin and serum Iron levels were significantly higher in the patient group (p<0.001 for all of them). Significant correlations existed between serum levels of TBARS, Uric acid, Ferritin and Iron levels in the patient group whereas only serum TBARS levels showed significant correlation with serum iron level in the control group. Regression analysis revealed that uric acid levels have a better predictive value (ß=0.3, p=0.001) than serum ferritin value (ß=0.013, p=0.871) for indicating TBARS production.

Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study.

AIMS: To report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. MATERIALS AND METHODS: Patients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan-Meier method and reported as 1-year estimates with 95% confidence intervals. RESULTS: Forty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50-66 years and a median baseline Karnofsky score of 60 (IQR = 50-60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan-Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7-51.1%) and 38.1% (95% confidence interval 25.9-56%), respectively. CONCLUSION: Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.

Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p < 0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p < 0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system.

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.

Atoltivimab/maftivimab/odesivimab (Inmazeb) combination to treat infection caused by Zaire ebolavirus.

Zaire ebolavirus has been responsible for several catastrophic outbreaks with a high mortality rate. Unfortunately, there were no approved therapies or vaccines to treat or prevent infections caused by Ebola virus (EBOV) or other filoviruses. Atoltivimab/ maftivimab/odesivimab (Inmazeb) is the first Food and Drug Administration (FDA)-approved treatment for Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who is reverse transcription polymerase chain reaction (RT-PCR)-positive for Zaire ebolavirus infection. The efficacy of Inmazeb has been established in vivo and it has successfully completed a phase I clinical trial in healthy individuals with no drug-related adverse effects. Additionally, Inmazeb has displayed significant reduction in mortality in the PALM (PAmoja tuLinde Maisha) trial, when compared with the control arm receiving ZMapp. Inmazeb has received orphan drug designation from both the U.S. FDA and the European Medicines Agency (EMA).

Update on nifurtimox for treatment of Chagas disease.

Chagas disease is a vector-borne neglected tropical disease caused by Trypanosoma cruzi. It is a systemic and chronic parasitic infection which is endemic in 21 countries with 10 million cases worldwide and 12,000 annual deaths. Around 70 million people in the Americas are at risk of contracting this disease, and less than 1% of infected people are treated due to low disease awareness and limited access to treatment. The current treatment for Chagas disease consists of benznidazole and nifurtimox under the World Health Organization (WHO) authorization protocol. The current treatment has limitations in terms of efficacy against the chronic phase of infection and side effects associated with prolonged therapy. This review provides an update on nifurtimox progress over the years and its recent approval by the U.S. Food and Drug Administration (FDA) in 2020 for the treatment of Chagas disease in pediatric patients under 18 years of age.

Experimental analyses of synergistic combinations of antibiotics with a recently recognised antibacterial agent, lacidipine.

The cardiovascular drug lacidipine (Lc) is known to possess antibacterial activity. Further potentiation of action is possible by synergism between Lc and an antibiotic or a non-antibiotic. The minimum inhibitory concentration (MIC) of antibiotics, Lc and other non-antibiotics were detected by the agar dilution technique in different bacteria. Synergism was determined by disc diffusion assay, the fractional inhibitory concentration (FIC) index through checkerboard assessment and, also, the protective capacity of the combination by administering the drugs along with 50 x LD(50) challenge dose of virulent Salmonella typhimurium in animal experiments. Synergism between Lc and penicillin was found to be statistically significant (P

Levonadifloxacin arginine salt to treat acute bacterial skin and skin structure infection due to S. aureus including MRSA.

Acute bacterial skin and skin structure infections (ABSSSIs) are one of the most common types of infections due to methicillin-resistant Staphylococcus aureus (MRSA). The standard of care for ABSSSI includes glycopeptides such as vancomycin, teicoplanin, oxazolidinones and fluoroquinolones, which are potent broad-spectrum antibacterial agents. Unfortunately, due to indiscriminate utilization, resistance to these agents is rising and identification of novel agents is an urgent unmet medical need. In this context, levonadifloxacin (WCK-771) is a novel, hydrate arginine salt of nadifloxacin with improved bactericidal activity against MRSA as well as fluoroquinolone-resistant S. aureus by targeting bacterial DNA supercoiling enzymes DNA gyrase and topoisomerase IV. Levonadifloxacin displays a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria, atypical bacteria, anaerobic bacteria and bioterror pathogens with a very low frequency of mutation. Levonadifloxacin also displays improved activity under low pH biofilm environments. The drug has successfully completed phase I, phase II and phase III clinical trials in India. The U.S. Food and Drug Administration (FDA) granted a Qualified Infectious Disease Product (QIDP) designation to levonadifloxacin for the treatment of MRSA infections in August 2014.

Pretomanid for the treatment of pulmonary tuberculosis.

Discovering novel drugs active against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is currently one of the most unmet medical needs. In this context, pretomanid (PA-824), a novel nitroimidazole prodrug that targets both replicating and nonreplicating cells, is being developed by TB Alliance under license from Novartis. In replicating Mtb, pretomanid inhibits mycolic acid biosynthesis, which is an important building block of Mtb cell wall. Under nonreplicating conditions, pretomanid is reduced by deazaflavin-dependent nitroreductase, leading to generation of reactive nitrogen species exhibiting potent antimycobacterial activity. The U.S. Food and Drug Administration (FDA) has approved pretomanid under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) for treatment of adult patients with treatment-intolerant or nonresponsive multidrug-resistant TB and extensively drug-resistant TB in combination with bedaquiline and linezolid as part of the oral.

Imipenem/cilastatin sodium/relebactam fixed combination to treat urinary infections and complicated intra-abdominal bacterial infections.

Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and ß-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.