LC-MS/MS: A sensitive and selective analytical technique to detect COVID-19 protein biomarkers in the early disease stage.

INTRODUCTION: The COVID-19 outbreak has put enormous pressure on the scientific community to detect infection rapidly, identify the status of disease severity, and provide an immediate vaccine/drug for the treatment. Relying on immunoassay and a real-time reverse transcription polymerase chain reaction (rRT-PCR) led to many false-negative and false-positive reports. Therefore, detecting biomarkers is an alternative and reliable approach for determining the infection, its severity, and disease progression. Recent advances in liquid chromatography and mass spectrometry (LC-MS/MS) enable the protein biomarkers even at low concentrations, thus facilitating clinicians to monitor the treatment in hospitals. AREAS COVERED: This review highlights the role of LC-MS/MS in identifying protein biomarkers and discusses the clinically significant protein biomarkers such as Serum amyloid A, Interleukin-6, C-Reactive Protein, Lactate dehydrogenase, D-dimer, cardiac troponin, ferritin, Alanine transaminase, Aspartate transaminase, gelsolin and galectin-3-binding protein in COVID-19, and their analysis by LC-MS/MS in the early stage. EXPERT OPINION: Clinical doctors monitor significant biomarkers to understand, stratify, and treat patients according to disease severity. Knowledge of clinically significant COVID-19 protein biomarkers is critical not only for COVID-19 caused by the coronavirus but also to prepare us for future pandemics of other diseases in detecting by LC-MS/MS at the early stages.

Metal-organic frameworks in chiral separation of pharmaceuticals.

Stereoselective chiral molecules are responsible for specific biological functions in nature. At present, more than half of the prescribed drugs are chiral. Living organisms display divergent pharmacological responses to the enantiomers, leading to altered toxicity, pharmacokinetics, and pharmacodynamics. Thus, chiral analysis, separation, and extraction are crucial for ensuring enantiomeric purity to develop safe and effective medication. In recent times, metal-organic frameworks (MOFs) with appealing structures are gaining importance because of their fascinating properties as a sorbent and stationary phase. MOFs are crystalline porous solid materials built by interconnecting metal ions or clusters and organic linkers. This review explores the advancements in MOFs for the isolation and separation of chiral active pharmaceutical drugs.

Impact of Cyanine Conformational Restraint in the Near-Infrared Range.

Appending conformationally restraining ring systems to the cyanine chromophore creates exceptionally bright fluorophores in the visible range. Here, we report the application of this strategy in the near-infrared range through the preparation of the first restrained heptamethine indocyanine. Time-resolved absorption spectroscopy and fluorescence correlation spectroscopy verify that, unlike the corresponding parent unrestrained variant, the restrained molecule is not subject to photoisomerization. Notably, however, the room-temperature emission efficiency and the fluorescence lifetime of the restrained cyanine are not extended relative to the parent cyanine, even in viscous solvents. Thus, in contrast to prior reports, the photoisomerization of heptamethine cyanines does not contribute significantly to the excited-state chemistry of these molecules. We also find that the fluorescence lifetime of the restrained heptamethine cyanine is temperature-insensitive and significantly extended at moderately elevated temperatures relative to the parent cyanine. Finally, computational studies have been used to evaluate the impact of the conformational restraint on atomic and orbital structure across the cyanine series. These studies clarify the role of photoisomerization in the heptamethine cyanine scaffold and demonstrate the dramatic effect of restraint on the temperature sensitivity of these dyes.

Cyanine Conformational Restraint in the Far-Red Range.

Far-red cyanine fluorophores find extensive use in modern microscopy despite modest quantum yields. To improve the photon output of these molecules, we report a synthetic strategy that blocks the major deactivation pathway: excited-state trans-to-cis polyene rotation. In the key transformation, a protected dialdehyde precursor undergoes a cascade reaction to install the requisite tetracyclic ring system. The resulting molecules exhibit the characteristic features of conformational restraint, including improved fluorescence quantum yield and extended lifetime. Moreover, these compounds recover from hydride reduction with dramatically improved efficiency. These observations enable efficient single-molecule localization microscopy in oxygenated buffer without addition of thiols. Enabled by modern organic synthesis, these studies provide a new class of far-red dyes with promising spectroscopic and chemical properties.

A Systematic Review of Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Following Coronavirus Disease 2019 Vaccination: A 2024 Update.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.

Acute Pancreatitis, Hypertriglyceridemia, and Diabetic Ketoacidosis: A Life-Threatening Triad.

Hypertriglyceridemia (HTG)-induced pancreatitis is a known complication of uncontrolled diabetes mellitus (DM). However, the coexistence of diabetic ketoacidosis (DKA) and acute pancreatitis in the presence of HTG is rare and presents diagnostic and therapeutic challenges. We present the case of a 42-year-old female with poorly controlled type 2 DM who developed severe HTG-induced pancreatitis complicated by DKA. She initially presented with abdominal pain, metabolic acidosis, and marked hyperglycemia. Subsequent investigations revealed significantly elevated serum triglyceride and lipase levels and characteristic findings of acute pancreatitis on imaging. This case report highlights the complex interplay of metabolic disturbances in diabetes and the importance of timely recognition and tailored management to achieve a successful outcome.

Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.

Uracil DNA-glycosylase (UNG) is a DNA repair enzyme that removes the highly mutagenic uracil lesion from DNA using a base flipping mechanism. Although this enzyme has evolved to remove uracil from diverse sequence contexts, UNG excision efficiency depends on DNA sequence. To provide the molecular basis for rationalizing UNG substrate preferences, we used time-resolved fluorescence spectroscopy, NMR imino proton exchange measurements, and molecular dynamics simulations to measure UNG specificity constants (kcat/KM) and DNA flexibilities for DNA substrates containing central AUT, TUA, AUA, and TUT motifs. Our study shows that UNG efficiency is dictated by the intrinsic deformability around the lesion, establishes a direct relationship between substrate flexibility modes and UNG efficiency, and shows that bases immediately adjacent to the uracil are allosterically coupled and have the greatest impact on substrate flexibility and UNG activity. The finding that substrate flexibility controls UNG efficiency is likely significant for other repair enzymes and has major implications for the understanding of mutation hotspot genesis, molecular evolution, and base editing.

A Systematic Review of COVID-19 Vaccine-Induced Takotsubo Cardiomyopathy: A 2023 Update.

Takotsubo cardiomyopathy (TCM) is a life-threatening transient left ventricular dysfunction triggered by either physical or emotional stressors. Concerns have been raised on reports of TCM after the coronavirus disease 2019 (COVID-19) vaccine. Our study provides comprehensive detail on COVID-19 vaccine-induced TCM. We conducted a systemic literature search using major databases, including PubMed, EMBASE, and Google Scholar up to November 2023, to identify cases of COVID-19 vaccine-induced TCM using the MeSH terms and keywords "covid-19 vaccines" and "takotsubo cardiomyopathy". We identified 15 case reports, including 16 patients with COVID-19 vaccine-induced TCM. The mean age was 55.81 ± 19.13 years, and 75% of the patients were female. The most common presentation was chest pain (62.5%), and the average time to first symptom onset was 3.12 ± 2.24 days. COVID-19 vaccine-induced TCM was reported in 43.75% of patients receiving the first and second dose each, and 87% of patients had messenger ribonucleic acid (mRNA) COVID-19 vaccine (Pfizer, Moderna). The elevated level of cardiac troponins was found in all the patients with a left ventricular ejection fraction (LVEF) of <50% in 15 patients, and T-wave inversion (50%) was the most common electrocardiographic finding. The mean length of the hospital stay was 7.27 ± 3.95 days, and 87% of patients were discharged. COVID-19 vaccine-induced TCM is a rare but life-threatening complication. TCM should be included in the differential diagnosis of chest pain or dyspnea in patients recently receiving the COVID-19 vaccine.

Sympathetic nerve blocks for posttraumatic stress disorder: an evidentiary review for future clinical trials.

Posttraumatic stress disorder (PTSD) is a chronic disorder resulting from exposure to traumatic events. In recent years, sympathetic nerve blocks have gained interest as an emerging treatment modality for PTSD. They have been shown to reduce autonomic dysfunction associated with PTSD symptoms, particularly in refractory and treatment-resistant patients. However, there is limited evidence regarding the technique's effectiveness in PTSD patients. Therefore, this scoping review was designed to update and summarize the current literature on this topic to inform the design of future clinical trials and studies. Our review of 22 studies (mostly case reports and series) included 1,293 PTSD patients who received sympathetic nerve blocks, primarily military service members and veterans, with a median age of 42.2 years. 0.5% Ropivacaine was the preferred anesthetic, and the right sided stellate ganglion block was the most commonly used technique. Relapse of symptoms was reported commonly, resulting in additional nerve block sessions. Most reported side effects were mild and transient. Despite the encouraging results, we remain cautious in interpreting the benefit of the technique due to the lack of sufficient standardized clinical trial data, heterogeneity in reported results, and the potential for bias in reporting. Future studies should focus on evaluating and addressing the technique's effectiveness, safety, tolerability, and indications.

Effectiveness of Injected Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcer Disease.

Objectives Platelet-rich plasma (PRP) has become quite a popular course of treatment and has tremendous healing properties. Our research question inquired about the effectiveness of injected formula of PRP as the cure for diabetic foot ulcer in comparison to the conventional dressing. Methodology  A prospective observational study was conducted at the Department of Diabetes and Endocrinology, Lady Reading Hospital, Peshawar, Pakistan, between July 2020 to January 2021. Patients' data were collected from the department's database after taking approval from the department. In our study, the selected patients were categorized into two equal groups - i.e. 80 cases in each group and were randomized by using randomization allocation software. In group I (study group) patients received PRP (1 ml /1 cm2) around the wound edges and in the base of the ulcer, while group II (control group) patients were treated with conventional dressing. Each patient was inspected for wounds on days 0, 14, 28, 90, and 180 on the basis of Wagner's classification of wounds to assess efficacy. A proforma was used to collect the required data and then utilized electronically for research analysis. Results The mean ± SD of age was 54.4±8.56 and 57.7±10.1 years in the injected PRP (study) and conventional dressing (control) groups, respectively. Of the 30 patients, 13 (43.3%) males and 17 (56.7%) females were enrolled in the study group, while 14 (46.7%) males and 16 (53.3%) females were included in the control group. The PRP was found effective in reducing the wound in about 64 (80%) patients, while wound dressing was effective in 37 (46.25%) patients (p<0.0001). In female patients, the wound healing was significantly better in the study group as compared to the control group (p<0.0001). Moreover, in patients aged above 55 years, frequently higher rates of wound reduction were observed in the study group as compared to the control group (p<0.0001).  Conclusion The study concluded that injected PRP was significantly better than conventional dressing in the management of diabetic foot ulcer. More clinical trials are necessary to evaluate the effectiveness of injected PRP to validate the current findings.

A Numerical Investigation on Hydrothermal Performance of Micro Channel Heat Sink with Periodic Spatial Modification on Sidewalls.

Electronic gadgets have been designed to incorporating very small components such as microcontrollers, electronic chips, transistors, microprocessors, etc. These components are exceptionally heat sensitive and can be wrecked if heat is not released. As a result, the thermal control of such components is critical to their optimum performance and extended life. The use of a microchannel heat sink (MCHS) has shown promising solutions to remove the excess heat. In this paper, we have proposed a novel design of MCHS and investigated it numerically. Four different surface modifications on the sidewall of the passage, namely, extended triangular surface (ETS), extended circular surface (ECS), triangular groove surface (TGS), and the circular groove surface (CGS) in the passage of the microchannel have been exploited in the Reynolds number of 100-900. In the presence of geometrical modification, the cooling capacities have been enhanced. The results show that the Nusselt numbers of ETS-MCHS, ECS-MCHS, TGS-MCHS, and CGS-MCHS are increased by 4.30, 3.61, 1.62, and 1.41 times in comparison to the Nusselt number of MCHS with smooth passage, while the friction factor values are increased by 7.33, 6.03, 2.74, and 1.68 times, respectively. In addition, the thermohydraulic performance parameter (THPP) has been evaluated and discussed. The fact that MCHS have THPP values greater than unity demonstrates that the passage's geometries are a practical means of achieving effective thermal management.

Effect of a Locally Tailored Clinical Pathway Tool on VBAC Outcomes in a Private Hospital in India.

BACKGROUND: Customized clinical and administrative interventions in the form of a care pathway tool can improve VBAC outcomes and reduce the alarming rise in caesarean sections globally. OBJECTIVE: To determine the effect of a locally tailored clinical pathway tool on VBAC outcomes in a private hospital in India. METHODS: A pre- and post-implementation study was conducted in a private hospital in India. All women with one previous caesarean section term pregnancy and cephalic presentation were included at baseline from January 2013 to December 2015 (Phase 1) and from January 2016 to December 2018 (Phase 2) after ongoing implementation of a clinical pathway tool by all providers. Background characteristics and clinical outcomes in both phases were reviewed retrospectively from case files. RESULTS: Overall 223 (13.42%) women among 1661 total births and 244 (11.62%) women among 2099 total births were included in Phase 1 and Phase 2, respectively. Total number of women who underwent trial of labour (TOLAC) increased from 36.77% to 64.34% (P < 0.001) and VBAC rate increased from 23.76% to 58.19% (P < 0.001) in Phase 2. There was no significant difference in perinatal morbidity and mortality in the two phases. CONCLUSION: A locally customized clinical care pathway tool implemented to support both mothers and care givers for TOLAC seemed to improve VBAC outcomes in a private setting in India.

Rationalising antibiotic use after low-risk vaginal deliveries in a hospital setting in India.

BACKGROUND: In 2017, a postoperative multidrug resistant case of urinary tract infection made obstetricians at Sitaram Bhartia Institute of Science and Research introspect the antibiotic usage in labouring mothers. Random case file reviews indicated overuse and variability of practice among care providers. This prompted us to explore ways to rationalise antibiotic use. METHODS: A multidisciplinary team of obstetricians, paediatricians and quality officers was formed to run this improvement initiative at a private hospital facility in India. Review of literature advocated formulating a departmental antibiotic policy. Creating this policy and implementing it using improvement methodology helped us rationalise antibiotic usage. INTERVENTIONS: We aimed to reduce the use of antibiotics from 42% to less than 10% in uncomplicated vaginal deliveries. We tested a series of sequential interventions using the improvement methodology of Plan-Do-Study-Act (PDSA) cycles, an approach recommended by the Institute for Healthcare Improvement. Learning from the PDSA cycle of the previous intervention helped decide the subsequent change ideas. The interventions included creation of a departmental antibiotic policy, staff engagement, and modification in documentation, concept of dual responsibility and team huddles as feedback opportunities. Information was analysed to understand the progress and improvement with change ideas. RESULTS: Background analysis revealed that antibiotic usage ranged from 24% to 69% and average rate of antibiotic prophylaxis was high (42.28%) in low-risk uncomplicated vaginal deliveries. The sequential changes resulted in reduction in antibiotic usage to 10% in the target population by 4 months. Sustained improvement was noted in the following months. CONCLUSION: We succeeded in implementing a departmental antibiotic policy aligning it with existing international guidelines and our local challenges. Antibiotic stewardship was one of the first major steps in our journey to avoid multidrug-resistant infections. Sustaining outcomes will involve continuous feedback to ensure engagement of all stakeholders in a hospital setting.

Extreme Orientational Uniformity in Large-Area Floating Films of Semiconducting Polymers for Their Application in Flexible Electronics.

Layer-by-layer fabrication of uniformly oriented thin films over large areas by cost-effective solution-based approaches can open new horizons for the realization of high-performance organic circuits in various applications. In this work, fabrication of a large-area ≈40 cm2 film with uniform orientation is reported for poly(3,3‴-dialkylquaterthiophene) (PQT) using a unidirectional floating film transfer method (UFTM). Orientation characteristics and charge transport anisotropy were analyzed using polarized UV-vis spectral mapping and fabrication of bottom-gated organic field-effect transistors (OFETs) from different regions. Films were found to be highly oriented with an optical dichroic ratio of ca. 15. Orientation characteristics reveal that films were highly oriented along the width of the film, covering >70% of the area, and angle-dependent field-effect mobilities are in good agreement with the orientation of the polymer backbones. These highly oriented films resulted in charge transport anisotropy of 8.9. An array of bottom-gated OFETs fabricated along the length of single large-area (≈15 × 2.5 cm2) thin film demonstrated the average field-effect mobility of 0.0262 cm2/(V s) with a very narrow standard deviation of 12.6%. We also demonstrated that film thickness can be easily tuned from 5.6 to 45 nm by increasing the PQT concentration, and field-effect mobility is highly reproducible even when the film thickness is 10 nm. Microstructural characterization of the thus-prepared large-area thin films revealed the edge-on stacked polymer backbones and surface roughness of <1 nm as probed by grazing incidence X-ray diffraction and atomic force microscopy, respectively. Flexible OFETs with bottom-gate top-contact geometry were also fabricated, having average field-effect mobility of 0.0181 cm2/(V s). There was no considerable change in mobility after bending the flexible devices at different radii.

Solvent-Assisted Friction Transfer Method for Fabricating Large-Area Thin Films of Semiconducting Polymers with Edge-On Oriented Extended Backbones.

Recent past has witnessed huge scientific efforts aiming toward enhancing in-plane charge transport by unidirectional orientation of conjugated polymer (CP) backbones adopting various techniques. However, in most of the existing methods, excess amounts of toxic halogenated solvents and preaggregation in solution are inevitable, which are the main bottlenecks toward large-scale fabrication. Solvent-assisted friction transfer (SAFT) is being reported as a novel method and improvisation over conventional friction transfer to expand its versatility. In this method, application of a small amount of the solvent (∼3 µL) during drawing not only leads to the entirely changed film morphology and molecular orientation but also addresses the existing substrate compatibility issues. Utilizing poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]-thiophene] as a representative CP under SAFT technique, films with extended backbone and edge-on orientation was successfully fabricated, which was confirmed by various characterization tools such as X-ray diffraction, polarized absorption, and polarized Raman spectroscopies. Further, anisotropic charge transport in these films was investigated by fabricating organic field-effect transistors and the role of contact resistance was also studied. Slight solvent use, compatibility with various substrates, and film fabrication with controlled orientation, and after validation of its generality on different CPs, SAFT can be expected to open new avenues in the area of printed electronics.

Investigation and Control of Charge Transport Anisotropy in Highly Oriented Friction-Transferred Polythiophene Thin Films.

Highly oriented thin films of poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT) were prepared by friction-transfer technique followed by their characterization using polarized absorption spectroscopy, angle-dependent polarized Raman spectroscopy, and X-ray diffraction (XRD) techniques. Orientation in high-molecular-weight (MW) polymers is hampered by chain folding or entanglements, which limit their macromolecular orientation. Interestingly, utilizing high-molecular-weight PBTTT (MW > 50 kDa) and friction-transfer technique, successful fabrication of highly oriented thin films with very high dichroic ratio (∼30) was demonstrated. The role of the substrate's surface energy and its impact on the field-effect mobility (µ) of the oriented thin films were comprehensively investigated. The influence of annealing the thin films as prepared on the bare and self-assembled monolayer (SAM)-treated SiO2 surfaces exhibiting differential trends of µ was systematically investigated. This was explained by partial and complete conformational transformation of macromolecules on bare and SAM-treated SiO2 surfaces, respectively, after annealing them beyond liquid crystalline phase transition temperature, as revealed by in-plane and out-of-plane XRD results. On bare SiO2, optimum µ up to 0.03 cm2 V-1 s-1 along the backbone orientation was obtained for the thin films annealed to 120 °C; whereas, it reached up to 0.36 cm2 V-1 s-1 on SAM-treated SiO2 after annealing at 200 °C. Finally, a charge transport mechanism was proposed taking evidence from the anisotropic optical and electrical characteristics of the friction-transferred PBTTT films into consideration.

Photophysical properties of the hemicyanine Dy-630 and its potential as a single-molecule fluorescent probe for biophysical applications.

Protein-induced fluorescence enhancement (PIFE) is an increasingly used approach to investigate DNA-protein interactions at the single molecule level. The optimal probe for this type of application is highly photostable, has a high absorption extinction coefficient, and has a moderate fluorescence quantum yield that increases significantly when the dye is in close proximity to a large macromolecule such as a protein. So far, the green-absorbing symmetric cyanine known as Cy3 has been the probe of choice in this field because the magnitude of the increase observed upon protein binding (usually 2-4 -fold) is large enough to allow for the analysis of protein dynamics on the inherently noisy single-molecule signals. Here, we report the characterization of the photophysical properties of the red-absorbing hemicyanine dye Dy-630 in the context of its potential application as a single-molecule PIFE probe. The behavior of Dy-630 in solution is similar to that of Cy3; the fluorescence quantum yield and lifetime of Dy-630 increase with increasing viscosity, and decrease with increasing temperature indicating the existence of an activated nonradiative process that depopulates the singlet state of the dye. As in the case of Cy3, the results of transient spectroscopy experiments are consistent with the formation of a photoisomer that reverts to the ground state thermally in the microsecond timescale. Unfortunately, experiments with DNA samples paint a more complex scenario. As in the case of Cy3, the fluorescence quantum yield of Dy-630 increases significantly when the dye interacts with the DNA bases, but in the case of Dy-630 attachment to DNA results in an already long fluorescence lifetime that does not provide a significant window for the protein-induced enhancement observed with Cy3. Although we show that Dy-630 may not be well-suited for PIFE, our results shed light on the optimal design principles for probes for PIFE applications.

Review of Maternal Mortality at a Tertiary Care Hospital: What Have we Achieved?

BACKGROUND: Mothers are the nurturing pillar of the family. When a woman dies or becomes ill, either during or after giving birth, the consequences have the potential to affect not only the woman herself, but her family, society and the nation as well. OBJECTIVES: The study was designed to evaluate the maternal mortality ratio in a tertiary care hospital, assess the demographic profile, causes of maternal mortality, type of delay, and to suggest remedial measures for improvement. METHODS: A retrospective study was done from Jan 2013 to Dec 2016 at a tertiary care hospital in New Delhi. The medical records of all maternal deaths over a period of 4 years were reviewed and analyzed. RESULTS: The Maternal mortality ratio in the study period was 361.71/100,000 live births. The number of maternal death was 364. Unbooked cases accounted for the majority, i.e., 322, booked being 29 and registered 13. Two hundred and eleven cases were referred from other centers. Maximum deaths occurred between 21 and 30 years (73.07%). Anemia was widely prevalent. Most maternal deaths were due to direct causes like hypertensive disorders (28.02%), pregnancy-related infections (20.87%), and hemorrhage (12.36%). Among indirect causes, anemia, hepatitis, heart disease and respiratory illness accounted for 15.93, 11.53, 3.29 and 5.49%, respectively. Type I delay was most common (64.28%). CONCLUSION: Strengthening of the peripheral centers, hiring competent staffs and adequate blood bank facilities together with reference linkages must be done. Auditing the causes for maternal mortality is extremely helpful to identify the preventable causes and delays.