Quantifying the risk of ectopic pregnancy with a transient diagnosis of pregnancy of unknown location.

OBJECTIVE: To quantify the risk of ectopic pregnancy among a transient diagnosis of pregnancy of unknown location (PUL). METHODS: Retrospective cohort study between August 2016 and November 2020. The final cohort included 244 patients with 255 PULs who presented with vaginal bleeding and/or abdominal pain, positive serum quantitative ß-human chorionic gonadotropin, and negative transvaginal ultrasound, with a subsequent definitive diagnosis. Two-way analysis of variance was used with significance set at P < 0.050. Bonferroni-corrected significance values were used in post hoc analysis. Multinominal logistic regression was used to predict adjusted risk for pregnancy outcome. RESULTS: Definitive diagnosis consisted of 101 (39%) intrauterine pregnancies, 33 (13%) ectopic pregnancies, and 121 (48%) resolved PULs or resolved/treated persisting PULs. A total 68% of the PULs subsequently became nonviable. Vaginal bleeding was associated with increased risk of nonuterine pregnancies. CONCLUSION: A total of 13% of PULs were subsequently diagnosed as ectopic pregnancies, which is higher than the 2% to 3% risk of an ectopic pregnancy in the general reproductive population. A total of 68% of PULs were subsequently nonviable, which is higher than the 31% early pregnancy loss rate in the general reproductive population. This study quantitatively confirms that a transient diagnosis of a PUL increases the odds for ectopic pregnancy and early pregnancy loss.

Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) and Its Mimics - A Single-Center Experience From a Tropical Setting.

OBJECTIVE: Identifying clinical and laboratory indicators that differentiate multisystem inflam-matory syndrome in children (MIS-C) apart from other febrile diseases in a tropical hospital setting. METHODS: Review of hospital records done in a tertiary care exclusive children's hospital for children admitted from April, 2020 till June, 2021. Laboratory values, severe acute respiratory syndrome coronavirus (SARS-CoV-2) serological status, and clinical signs and symptoms of patients with MIS-C, and those with similar presentations were analyzed. RESULTS: 114 children fulfilled the inclusion criteria (age group of 1 mo-18 y) for whom a diagnosis of MIS-C was considered in the emergency room based on the clinical features. Among them, 64 children had the final diagnosis of MIS-C, and the remaining 50 children had confirmatory evidence of infections mimicking MIS-C such as enteric fever, scrub typhus, dengue and appendicitis. CONCLUSION: Older age group, presence of muco-cutaneous symptoms, very high C-reactive protein, neutrophilic leukocytosis, abdominal pain and absence of hepatosplenomegaly favor a diagnosis of MIS-C.

Crystal structure analysis of pyrrolidone carboxyl peptidase from Thermus thermophilus.

Pyrrolidone carboxyl peptidase (PCP) hydrolytically removes the L-pyroglutamic acid from the amino terminal region of pyroglutamyl proteins or peptides. So far, only a limited number of structures of PCP have been solved. Here we report the crystal structure of pyrrolidone carboxyl peptidase from Thermus thermophilus (TtPCP) which has been solved using the molecular replacement method and refined at 1.9 Å resolution. TtPCP follows the α/ß/α architecture in which the central ß-sheets are surrounded by α-helices on both sides. The inter subunit contact between two monomers consists of two short antiparallel ß-strands and part of a long protrusion loop. By comparing the TtPCP with its structural homologs, we identified the putative catalytic triad residues as Glu76, Cys139 and His160. A unique disulfide link found in some homologs of TtPCP, formed between two monomers that provide thermal stability to the protein, is not observed in TtPCP. Hence, being a thermophilic protein, the putative thermal stability of TtPCP could be due to more intra and inter-molecular hydrogen bonds, hydrophobic and ion pair interactions when compared with its mesophilic counterpart. The structural details of TtPCP will be helpful to understand the basis of the intrinsic stability of thermophilic proteins. Also, it could be useful for protein engineering.

Development of a Novel, Low-Cost, Low-Fidelity Simulation Model for Pudendal Nerve Block Application.

Background: Pudendal nerve block is an important alternative to neuraxial anesthesia, yet studies demonstrate that 3% to 50% of pudendal nerve blocks are ineffective. Lack of clinician training is the most common cause, and there are no simulation models currently described. Objective: To develop and test a novel, low-cost, low-fidelity simulation model for training residents in the placement of a pudendal nerve block. Methods: A pudendal nerve block model was developed using commonly found supplies, with a cost of $20.57. First-year to fourth-year obstetrics and gynecology (OB/GYN) and family medicine (FM) residents were invited to 1 of 4 pudendal nerve block 1-hour simulation sessions from December 2019 to March 2021 during their required teaching sessions. Expert faculty led a discussion of pudendal nerve blocks, then participants practiced with the described model. A survey about the model was created by the authors and administrated prior to and immediately after the session. Pre- and post-surveys were analyzed by Wilcoxon signed rank tests, and Bonferroni correction was performed. Results: Thirty-four out of a total of 36 eligible residents participated (94%). Residents showed improvement in knowledge (median pre-simulation score 43.99 compared with 70.06 post-simulation, P<.00625) and self-assessed confidence (median pre-simulation score 1.7 compared with 3.2 post-simulation, P<.00625) of a pudendal block placement after simulation training. Conclusions: This new, low-cost, reusable, low-fidelity simulation model for pudendal nerve block placement improved knowledge and confidence in OB/GYN and FM residents after 1 hour of simulation training.

Diagnostic Spectrum and Clinical Profile of Primary Immunodeficiency Disorders at a Tertiary Care Children Hospital in Southern India.

BACKGROUND: Primary immunodeficiency disorders are genetically heterogeneous immune disorders with a wide range of infectious and non-infectious manifestations. OBJECTIVE: To describe a single-center experience of primary immunodeficiency disorders. DESIGN: Retrospective analysis from January 2015 to January 2020. SETTING: Tertiary care children's hospital. PARTICIPANTS: One hundred and twelve children (<18 years) diagnosed with primary immunodeficiency disorders. OUTCOME MEASURE: Diagnostic spectrum, clinical features, and outcome. RESULTS: The median (IQR) age of the first clinical manifestation and lag time in diagnosis was 10 (27) and 11 (18) months, respectively. Twenty-seven children (24%) were diagnosed during their first presentation. Thirty-six (32%) children had phagocytic disorders, 20 (17.8%) had combined/cellular defects, 18 (16%) had predominant antibody deficiencies and 17 (15%) had disorders of immune dysregulation. Non-infectious manifestations were seen in 54 (48%). Eight children underwent hematopoietic stem cell transplantation, 44 (39%) children were on antimicrobial prophylaxis and supportive therapy, 36 (32%) were lost to follow-up and 24 (21%) children died. CONCLUSION: Congenital defects of phagocyte function, followed by combined/cellular defects are the commonest primary immune deficiencies (PIDs) identified in southern India. Long lag time in diagnosis and high mortality in our cohort emphasizes the need for early diagnosis and early referral.

Epidemiological and Clinical Profile of Pediatric Inflammatory Multisystem Syndrome - Temporally Associated with SARS-CoV-2 (PIMS-TS) in Indian Children.

Background: We describe the demographic, clinical and labo-ratory findings along with the treatment and outcomes among children meeting the case definition of Pediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We analyzed the clinical and laboratory findings of children who presented with PIMS-TS during an 8-week period from May 4, 2020 to July 8, 2020. RESULTS: We report 19 children with a median age of 6 year (IQR: 13 months-16 years), who met the case definition of PIMS-TS. All of them presented with fever. Multi organ involvement (79%), mucocutaneous involvement (74%), cardiovascular symptoms (63%) and gastrointestinal symptoms (42%) were the other features. Elevated levels of C-reactive protein was found in all of them and the majority of them had evidence of coagulopathy; intensive care admissions were needed in 12 (63%) and vasoactive medications were given to 6 (31.5%) children. There were no deaths. CONCLUSION: Children with PIMS-TS present with a wide range of signs and symptoms. Fewer children in this series had coronary artery abnormalities, and there was a low incidence of RT-PCR positivity with high presence of SARS-CoV-2 antibodies.

Antagonistic effect of ursolic acid on Staphylococcal biofilms.

AIM: The present study was carried out to study the effect of ursolic acid (UA) as a potential anti-biofilm agent in dispersing the biofilm generated by Staphylococcus aureus isolated from milk samples of crossbred dairy cows on the day of drying. Further, in the S. aureus isolates, the presence of intracellular adherence gene locus involved in biofilm production (icaD) was investigated. MATERIALS AND METHODS: A total of 50 S. aureus strains were isolated over a period of 3 months from 200 milk samples collected from crossbred dairy cows on the day of drying. These isolates were subjected for biofilm detection by Congo red agar (CRA), microtiter plate assay (MTP), and polymerase chain reaction specific for icaD gene. The antagonistic effect of biofilm formation by UA was studied using different concentrations (30 µg/ml and 60 µg/ml) of UA and compared with the control group. RESULTS: Among the 50 S. aureus subjected for biofilm detection, 34 and 40 isolates were detected as biofilm agents by CRA and MTP methods, respectively. The in vitro studies on the effect of UA in inhibiting biofilm formation by S. aureus using MTP assay showed 71.5% and 48.6% inhibition at UA concentrations of 60 µg/ml and 30 µg/ml, respectively, with a significant difference (p<0.05) between the treated and untreated isolates, which was further evident by scanning electron microscopy. Interestingly, the isolates that were tested to be resistant through Antibiotic Sensitivity Test to commonly used antibiotics were found to be sensitive to all the tested antibiotics following UA treatment at both the tested concentrations. Furthermore, molecular detection of icaD gene for biofilm detection revealed that all the isolates that were positive by MTP had icaD gene. CONCLUSION: Increased incidence of biofilm agents in dairy infections must be considered as an alarming situation. UA treatment significantly enhanced the sensitivity of the microbial pathogens to commonly used antibiotics. Hence, attention must be paid toward implementation of new strategies such as therapeutic regimes with a combination of antibiotic and anti-biofilm agents for effective treatment of infections in dairy farms.

Rapid antigen diagnostic testing for the diagnosis of group A beta-haemolytic streptococci pharyngitis.

Background: It is difficult to make a diagnosis of group A beta-haemolytic streptococci (GABHS) pharyngitis solely on clinical findings. The McIssac scoring system has been recommended as a reliable clinical tool for diagnosis. The rapid antigen detection test (RADT) has been shown to considerably increase the number of patients who are appropriately treated for streptococcal pharyngitis, compared with the use of traditional throat cultures. It also reduces the time to start treatment. We evaluated the diagnostic utility of RADT in comparison with throat swab culture. Methods: Using the McIssac scoring system, RADT and throat swab cultures in those with a McIssac score of 3 or more, we evaluated 165 children (aged 2-15 years) with a clinical diagnosis of pharyngitis. Results: GABHS pharyngitis was confirmed in 41 (24.8%) by throat swab culture and RADT was positive in 39(23.6%). Only in 2 (4.9%) children, RADT was negative but throat swab was positive. The sensitivity of RADT was 89.7% and specificity was 98.4% with a positive predictive value of 94.6%, negative predictive value of 96.9% and diagnostic accuracy of 96.4%. Conclusion: RADT performed was observed to have high sensitivity and sensitivity for the diagnosis of GABHS pharyngitis in contrast to an earlier report from India. Our observations suggest that using RADT as a point-of-care test is reliable and cost-effective and needs to be propagated in Indian settings where facilities for throat swab culture are not routinely available and also because clinical diagnosis based on scoring systems are comparatively less reliable.

Crystal structure of [4-(chloro-meth-yl)phen-yl](4-hy-droxy-piperidin-1-yl)methanone.

The title compound, C13H16ClNO2, crystallized with two independent mol-ecules in the asymmetric unit (A and B). The piperidinol ring in mol-ecule B is disordered over two positions with a site occupancy ratio of 0.667 (5):0.333 (5). In both mol-ecules these rings have a chair conformation, including the minor component in mol-ecule B. Their mean planes are inclined to the benzene ring by 45.57 (13)° in mol-ecule A, and by 50.5 (4)° for the major component of the piperidine ring in mol-ecule B. In the crystal, the individual mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains of A and B mol-ecules along the [100] direction. The chains are inter-linked by C-H⋯O hydrogen bonds, forming ribbons.

Crystal structure of (4-hy-droxy-piperidin-1-yl)[4-(tri-fluoro-meth-yl)phen-yl]methanone.

The title compound, C13H14NO2F3, crystallises with two mol-ecules, A and B, in the asymmetric unit, with similar conformations. The dihedral angles between the piperidine and phenyl rings are 83.76 (2) and 75.23 (2)° in mol-ecules A and B, respectively. The bond-angle sums around the N atoms [359.1 and 359.7° for mol-ecules A and B, respectively] indicate sp (2) hybridization for these atoms. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into separate [100] chains of A and B mol-ecules. The chains are cross-linked by C-H⋯O inter-actions, generating alternating (001) sheets of A and B mol-ecules.

Crystal structure of (4-hy-droxy-piperidin-1-yl)(4-methyl-phen-yl)methanone.

In the title compound, C13H17NO2, the dihedral angle between the planes of the piperidine and benzene rings is 51.7 (2)°. The bond-angle sum around the N atom [359.8 (3)°] indicates sp (2) hybridization of the atom. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules, forming chains along [001].

Crystal structure of the adduct (4-chloro-phen-yl)(4-hy-droxy-piperidin-1-yl)methanone-(4-chloro-phen-yl)(piperidin-1-yl)methanone (0.75/0.25).

In the title compound, 0.75C12H14ClNO2·0.25C12H14ClNO, which is an adduct comprising 0.75 4-hy-droxy-piperidin-1-yl or 0.25 4-piperidin-1-yl substituents on a common (4-chloro-phen-yl)methanone component; the dihedral angles between the benzene ring and the two piperidine rings are 51.6 (3) and 89.5 (7)°, respectively. The hy-droxy-piperidine ring is in a bis-ectional oriention (bi) with the phenyl ring. In the crystal, inter-molecular O-H⋯O hydrogen bonds between the hy-droxy-piperidine group and the keto O atom lead to the formation of chains extending along the c- axis direction.

Chromhidrosis--colored sweat in a toddler.

BACKGROUND: Chromhidrosis means production of coloured sweat. CASE CHARACTERISTICS: A toddler who presented with colored sweat was diagnosed to have chromhidrosis based on skin biopsy. No treatment was attempted considering the young age. OUTCOME: Parents were counselled about the benign nature of this disorder. MESSAGE: Identification of causes of colored sweat requires appropriate investigations.

Predictors of coronary artery aneurysms in Kawasaki disease.

Kawasaki disease (KD) is a common cause of cardiovascular morbidity in young children. No study has attempted to stratify risk factors for coronary artery involvement in Indian children. We attempted to study prospectively the risk factors for coronary involvement in children with KD in a tertiary care hospital between October 2009 and November 2011. The clinical details and investigations for all children admitted with KD were tabulated, and echocardiography was performed; 37 children were admitted with KD; and 8 children (21%) had coronary artery abnormalities. Prolonged fever, wider dispersion of symptoms, and pyuria were significantly associated with the development of coronary lesions. Clinical factors such as wider dispersion of symptoms and prolonged fever along with presence of pyuria can increase the risk of coronary lesions. The presence of these factors may help direct aggressive management and prevent loss of precious time.

Gamma interferon receptor defect presenting as recurrent tuberculosis.

Failure of response to therapy in childhood tuberculosis may be due to resistance, paradoxical response or immunodeficiency. Interferon-γ (IFNγ) plays a major role during host defense against Mycobacterium tuberculosis (Mtb). An 8-y-old boy presented with fever, hepatosplenomegaly and parotid abscess. He had been earlier treated for BCG adenitis in infancy and at 5 y for TB osteomyelitis of iliac bone and recovered. Investigations confirmed disseminated Mycobacterium Avium Intracellulare infection. He was investigated for immunodeficiency because of recurrent mycobacterial disease and a partial defect of γ-interferon receptor was identified. He required a 2 y course of therapy with a 7 drug regimen and recovered. The authors report this case because of its rarity and to highlight the need to consider γ-interferon receptor defect in the presence of recurrent tuberculosis (TB) and also review the options for therapy.

Vitamin D deficiency in childhood-a review of current guidelines on diagnosis and management.

Vitamin D deficiency has emerged as a significant public health problem throughout the world. Even in the Indian context,it has been reported to be present in majority of children in spite of wide availability of sunlight. Recent guidelines have defined vitamin D status as severe deficiency, deficiency, sufficiency and risk for toxicity as 25(OH)D levels <5, <15, >20 and >50ng/mL, respectively.The manifestations of deficiency may vary from hypocalcemic seizures, tetany in infancy and adolescence to florid rickets in toddlers. Treatment is necessary for all individuals with deficiency whether symptomatic or not and consists of vitamin D supplementation as Stoss therapy or daily or weekly oral regimens with equal efficacy and safety, combined with calcium supplements. Routine supplementation starting from newborn period is being increasingly endorsed by various international organizations. Prevention by sensible sunlight exposure, food fortification and routine supplementation are the currently available options for tackling this nutritional deficiency.

Differentiation of Staphylococcus aureus and Staphylococcus epidermidis by PCR for the fibrinogen binding protein gene.

Mastitis is one of the most common and burdensome diseases afflicting dairy animals. Among other causes of mastitis, staphylococci are frequently associated with clinical and subclinical mastitis. Although Staphylococcus aureus is the predominant species involved, Staphylococcus epidermidis and other coagulase-negative staphylococci are increasingly being isolated from cases of bovine mastitis. Although Staph. aureus and Staph. epidermidis can be easily differentiated based on their biochemical properties, such phenotypic identification is time consuming and laborious. This study aimed to rapidly identify Staph. aureus and Staph. epidermidis. Accordingly, a multiplex PCR was developed and we found that a single gene encoding the adhesin fibrinogen binding protein could be used to identify and differentiate the two species. Consequently, a multiplex reaction combining a triplex PCR for Staph. aureus and a duplex PCR for Staph. epidermidis was standardized, first using bacterial cultures and then with pasteurized milk spiked with live organisms or DNA extracted from the organisms. The test could specifically detect Staph. aureus and Staph. epidermidis even in the presence of a dozen other organisms. The limit of detection for detecting Staph. aureus and Staph. epidermidis separately was 10 to 100 cfu/mL for simplex PCR and 10(4)cfu/mL for multiplex PCR. Conversely, the limit was 10(6)cfu/mL by multiplex PCR for simultaneous detection of both the organisms when spiked into culture medium or pasteurized milk. Overnight enrichment enhanced the assay sensitivity 100-fold. The assay had a high diagnostic sensitivity and specificity. The application of the test was verified on 602 field isolates of staphylococci that had been characterized earlier by phenotypic methods. Importantly, 25 coagulase-negative isolates were identified as Staph. aureus by the multiplex PCR. The test could be adapted for use in clinical diagnostic laboratories.