Implementation and evaluation of the public health emergency response to the 2019 outbreak of e-cigarette and vaping product use-associated lung injury in Massachusetts,USA.

OBJECTIVES: In 2019, an outbreak of e-cigarette/vaping product use-associated lung injury (EVALI) across the United States was responsible for acute harm, hospitalizations, and mortality among individuals using vape products, including youth and young adults. The objective of this study is to describe and evaluate the public health surveillance and emergency response activities that occurred in Massachusetts during the 2019 EVALI outbreak. STUDY DESIGN: Descriptive process and policy evaluation. METHODS: Between September and December 2019, the Massachusetts Department of Public Health temporarily removed access to e-cigarettes in stores, conducted tobacco retailer educational activities, and promoted tobacco cessation communications. The public health response was monitored through online adult panel surveys, in-school youth surveys, retailer compliance checks, and existing tobacco control program surveillance. RESULTS: Massachusetts residents indicated high awareness of the EVALI outbreak and the corresponding public health response. Tobacco retailers were compliant with the temporary state prohibition on the sale of e-cigarettes. In response to reduced access to vaping products in stores, both adult and youth survey respondents reported reduced use, increased quit attempts, or complete e-cigarette cessation. CONCLUSION: Emergency action undertaken by state public health programs and other governmental agencies corresponded with reduced availability of e-cigarettes and an increase in self-reported quit behaviors. Existing public health infrastructure at the state and local levels in Massachusetts facilitated an environment in which emergency and permanent protective measures could be implemented.

Role of chest radiograph in predicting the need for ventilator support in COVID-19 patients.

Background: COVID-19 disease, a pandemic for more than two years, has major morbidity and mortality related to pulmonary involvement. Chest radiography is the main imaging tool for critically ill patients. As the availability of arterial blood gas analysis is limited in the Level I and II healthcare centres, which are major partners in providing healthcare in resource-limited times, we planned the present study. Objectives: To assess the role of chest radiography in predicting the need for oxygen/ventilator support in critically ill COVID-19 patients. Methods: This hospital-based, retrospective study included 135 patients who needed oxygen/ventilator support and had optimal-quality chest radiographs at admission. All the chest X-rays were evaluated and a severity score was calculated on a predesigned pro forma. Statistical evaluation of the data obtained was done using appropriate tools and methods. Results: Males outnumbered females, with a mean age of 54.35 ± 14.49 years. More than 72% of patients included in our study needed ventilator support while the rest needed oxygen support. There was a significant statistical correlation between the chest radiograph severity score and SPO2 /PaO2 levels in our study. Using a cut-off value >8 for the chest radiograph severity score in predicting the need for ventilator support in a Covid-19 patient, the sensitivity, specificity and accuracy was 85.7%, 92.5% and 89.5%, respectively. Conclusion: Chest radiography remains the mainstay of imaging in critically ill COVID-19 patients when they are on multiple life-support systems. Though arterial blood gas analysis is the gold standard tool for assessing the need for oxygen/ventilator support in these patients, the severity score obtained from the initial chest radiograph at the time of admission may also be used as a screening tool. Chest radiography may predict the need for oxygen/ventilator support, allowing time for patients to be moved to an appropriate-level healthcare centre, thus limiting morbidity and mortality.

Hypercapnia-induced vasodilation in the cerebral circulation is reduced in older adults with sleep-disordered breathing.

The prevalence of sleep-disordered breathing (SDB) is higher in older adults compared with younger individuals. The increased propensity for ventilatory control instability in older adults may contribute to the increased prevalence of central apneas. Reductions in the cerebral vascular response to CO2 may exacerbate ventilatory overshoots and undershoots during sleep. Thus, we hypothesized that hypercapnia-induced cerebral vasodilation (HCVD) will be reduced in older compared with younger adults. In 11 older and 10 younger adults with SDB, blood flow velocity in the middle cerebral artery (MCAV) was measured using Doppler transcranial ultrasonography during multiple steady-state hyperoxic hypercapnic breathing trials while awake, interspersed with room air breathing. Changes in ventilation, MCAV, and mean arterial pressure (MAP) via finger plethysmography during the trials were compared with baseline eupneic values. For each hyperoxic hypercapnic trial, the change (Δ) in MCAV for a corresponding change in end-tidal CO2 and the HCVD or the change in cerebral vascular conductance (MCAV divided by MAP) for a corresponding change in end-tidal CO2 was determined. The hypercapnic ventilatory response was similar between the age groups, as was ΔMCAV/Δ[Formula: see text]. However, compared with young, older adults had a significantly smaller HCVD (1.3 ± 0.7 vs. 2.1 ± 0.6 units/mmHg, P = 0.004). Multivariable analyses demonstrated that age and nadir oxygen saturation during nocturnal polysomnography were significant predictors of HCVD. Thus, our data indicate that older age and SDB-related hypoxia are associated with diminished HCVD. We hypothesize that this impairment in vascular function may contribute to breathing instability during sleep in these individuals.NEW & NOTEWORTHY This study demonstrates, for the first time, in individuals with sleep-disordered breathing (SDB) that aging is associated with decreased hypercapnia-induced cerebral vasodilation (HCVD). In addition to advanced age, the magnitude of nocturnal oxygen desaturation due to SDB is an equal independent predictor of HCVD.

Evaluation of biliary complications on magnetic resonance cholangiopancreatography and comparison with direct cholangiography after living-donor liver transplantation.

AIM: To evaluate the imaging characteristics of biliary complications following liver transplantation on magnetic resonance cholangiopancreatography (MRCP) and its diagnostic accuracy in comparison with direct cholangiography. MATERIAL AND METHODS: In this prospective study, 34 patients being evaluated for possible biliary complications after living-donor liver transplantation (LDLT) with abnormal MRCP findings were followed up for information regarding direct cholangiography either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) within 7 days of MRCP. Twenty-nine patients underwent ERCP and five patients underwent PTC. RESULTS: Compared to findings at direct cholangiography, MRCP presented 96.9% sensitivity, 96.9% positive predictive value, and 94.1% accuracy for the detection of biliary complications. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of anastomotic strictures, biliary leak, and biliary stone or sludge on MRCP was found to be 100%, 84.6%, 91.3%, 100% and 94.1%; 72.7%, 95.7%, 88.9%, 88% and 88.2%; 80%, 100%, 100%, 96.7% and 97.1%, respectively. CONCLUSION: MRCP is a reliable non-invasive technique to evaluate the biliary complications following LDLT. MRCP should be the imaging method of choice for diagnosis in this setting and direct cholangiography should be reserved for cases that need therapeutic interventions.

Evolution of ramucirumab in the treatment of cancer - A review of literature.

Ramucirumab is a recombinant human monoclonal antibody and is used in the treatment of advanced malignancies. Its mechanism of action is by inhibiting angiogenesis in tumor cells by targeting the vascular endothelial growth factor receptor 2. United States Food and Drug Administration (FDA) approved it initially in 2014 for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma and metastatic non-small cell lung carcinoma. It was approved by FDA in 2015 for the treatment of advanced colorectal cancer. This manuscript consolidates pre-clinical trials to phase I, II, and III trial data indicating the effects of ramucirumab on different cancer types, which led to its approval. By comparing these clinical trials alongside each other, we can more easily examine the studies that have already been completed, along with currently ongoing studies and potential further areas of interest for this newly approved treatment. This approach makes it convenient to compare dosages, overall survival, adverse events, as well as possible routes for combination therapy with ramucirumab. By compiling results for various oncological malignancies, we can differentiate between treatments that are effective and have the highest incidence of stable disease, and those that do not seem promising. Ramucirumab has been effective in the treatment of various carcinomas and this article outlines other tumors in which this treatment option may be successful.

Adjuvant therapies using normobaric oxygen with hypothermia or ethanol for reducing hyperglycolysis in thromboembolic cerebral ischemia.

BACKGROUND AND PURPOSE: Normobaric oxygen (NBO), ethanol (EtOH), and therapeutic hypothermia (TH) delivered alone or in combination have neuroprotective properties after acute stroke. We used an autologous thromboembolic rat stroke model to assess the additive effects of these treatments for reducing the deleterious effects of hyperglycolysis post-stroke in which reperfusion is induced with recombinant tissue plasminogen activator (rt-PA). METHODS: Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion with an autologous embolus. One hour after occlusion, rt-PA was administered alone or with NBO (60%), EtOH (1.0 g/kg), TH (33 °C), either singly or in combination. Infarct volume and neurological deficit were assessed at 24h after rt-PA-induced reperfusion with or without other treatments. The extent of hyperglycolysis, as determined by cerebral glucose and lactate levels was evaluated at 3 and 24h after rt-PA administration. At the same time points, expressions of glucose transporter 1 (Glut1), glucose transporter 3 (Glut3), phosphofructokinase1 (PFK-1), and lactate dehydrogenase were (LDH) measured by Western blotting. RESULTS: Following rt-PA in rats with thromboembolic stroke, NBO combined with TH or EtOH most effectively decreased infarct volume and neurological deficit. As compared to rt-PA alone, EtOH or TH but not NBO monotherapies significantly reduced post-stroke hyperglycolysis. The increased utilization of glucose and production of lactate post-stroke was prevented most effectively when NBO was combined with either EtOH or TH after reperfusion with rt-PA, as shown by the significantly decreased Glut1, Glut3, PFK-1, and LDH levels. CONCLUSIONS: In a rat thromboembolic stroke model, both EtOH and TH used individually offer neuroprotection after the administration of rt-PA. While NBO monotherapy does not appear to be effective, it significantly potentiates the efficacy of EtOH and TH. The similar neuroprotection and underlying mechanisms pertaining to the attenuation of hyperglycolysis provided by EtOH or TH in combination with NBO suggest a possibility of substituting EtOH for TH. Thus a combination of NBO and EtOH, which are widely available and easily used, could become a novel and effective neuroprotective strategy in the clinical setting.

Sun-screening bioactive compounds mycosporine-like amino acids in naturally occurring cyanobacterial biofilms: role in photoprotection.

AIMS: To investigate the occurrence of UV sunscreening biomolecules and their role in photoprotection in cyanobacterial biofilms growing in brightly lit habitats with high UV fluxes. METHODS AND RESULTS: High performance liquid chromatography with photodiode-array and mass spectrometry revealed the presence of mycosporine-like amino acids (MAAs) shinorine (λ(max) 334 nm, m/z 333), porphyra-334 (λ(max) 334 nm, m/z 347), mycosporine-glycine (λ(max) 310 nm, m/z 246) and palythinol (λ(max) 332 nm, m/z 303). Two unknown MAAs with λ(max) at 320 (m/z 289) and 329 nm (m/z 318) were also found. Biosynthesis of MAAs was found to increase with increase in exposure time under UV radiation. The MAAs from biofilms showed efficient radical scavenging activity as well as photoprotective potential on the survival of UV-treated Escherichia coli cells. CONCLUSIONS: Biosynthesis of photoprotectants is an important mechanism to prevent photodamage in Cyanobacteria. UV-induction and photoprotective function of MAAs may facilitate them to perform important ecological functions under harsh environmental conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: There are very few reports on qualitative and quantitative characterization of different MAAs in cyanobacterial biofilms. Due to strong UV absorption and photoprotective function, MAAs may be used as an active ingredient in cosmetic and other pharmaceutical industries.

Comparison of measurement properties of the P4 pain scale and disease specific pain measures in patients with knee osteoarthritis.

OBJECTIVE: To compare measurement properties of the P4 pain scale, Western Ontario and McMaster Universities Arthritis Index pain subscale (WOMAC-pain), and Intermittent and Constant Osteoarthritis Pain (ICOAP) measure in patients with knee osteoarthritis (OA). DESIGN: A secondary analysis from a randomized controlled trial included participants (n = 156) with knee OA that were consulting with a surgeon regarding knee arthroplasty. They completed pain measures (P4, WOMAC-pain, ICOAP) and WOMAC-function subscale (WOMAC-function) at baseline and 2 weeks. Measurement properties assessed in various subgroups included floor/ceiling effects, test-retest reliability using intraclass correlation coefficients (ICC2,1), internal consistency using Cronbach's ɑ, factorial structure of each pain measure combined with WOMAC-function using principal component analysis, and responsiveness using standardized response mean (SRM). RESULTS: P4 had low floor and ceiling effects (<1%). P4 test-retest reliability (ICC2,1 = 0.72), internal consistency (Chronbach's ɑ = 0.91), and responsiveness (SRM = 0.56) were similar to the values for WOMAC-pain and ICOAP. Factorial structure of P4 and ICOAP were separate from WOMAC-function items. WOMAC-pain and WOMAC-function items loaded on similar factors. ICOAP-constant subscale had a large floor effect (33%). CONCLUSIONS: P4 should be used to measure pain in patients with knee OA. It had acceptable measurement properties which is comparable to more widely used pain measures. WOMAC-pain shared a factorial structure with WOMAC-function indicating these measures might be capturing the same construct, questioning its validity to measure pain separately from function. ICOAP had acceptable properties. More work should compare pain measures in less severely affected OA populations.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Variations in the formation of the median nerve and its clinical correlation.

Variations in the formation of the median nerve are of interest to anatomists, radiologists, and surgeons. These variations may be vulnerable to damage in surgical operations, but their knowledge also helps in the interpretation of a nervous compression having unexplained clinical symptoms. We studied the variation in the formation of the median nerve in 87 cadavers, i.e. 174 upper limbs of formalin preserved cadavers at the department of Anatomy, Subharti medical college. We observed an additional root taking part in the formation of the median nerve in 26.4% of upper limbs, unusual low formation of the median nerve in the arm in front of the brachial artery in 18.4% of upper limbs, and median nerve formation medial to the axillary artery in 10.3% of upper limbs. Knowledge of such anatomical variations is of interest to the anatomist and clinician alike. Surgeons who perform procedures involving neoplasm or trauma repair need to be aware of these variations.

Variant origin of superior polar artery and unusual hilar branching pattern of renal artery with clinical correlation.

Classically, a single renal artery arising from the abdominal aorta supplies the respective kidney on each side. Near the hilum of the kidney each renal artery divides into anterior and posterior branchs, which in turn divide into segmental arteries supplying the different renal segments. A total of 84 formalin fixed cadavers (73 male and 11 female, 168 kidneys in total) constituted the material for the study. During routine abdominal dissection conducted for medical undergraduates, the kidneys and their arteries were explored and variations in morphological patterns of renal arteries were noted. We observed superior polar renal artery in 22.6% cases. Superior polar renal arteries had different sources of origin. In 10.7% of cases it came directly from the abdominal aorta as an accessory renal artery; in 5.4% of cases as a direct branch from the main renal artery; in 3.6% of cases from the superior hilar renal artery (from one of the duplicated renal arteries); and in 3.0% of cases from a segmental branch of the renal artery. We also observed unusual hilar branching patterns of renal arteries, which included a fork pattern in 11.3% of cases, ladder pattern in 7.7% of cases, net pattern in 5.9% of cases, and triplicate in 3.0% of cases. Understanding the anatomy of vascular variations of the kidney is essential for the clinician to be able to perform procedures such as renal transplantation, interventional radiological procedures, and renal vascular operations more safely and efficiently.

Fractal growth kinetics and electric potential oscillations during electropolymerization of pyrrole.

Fractal growth, growth kinetics, and electrical conductivity of aggregates obtained during electropolymerization in the systems (A) pyrrole-4-toluene sulfonic acid silver salt (4-TSS)-acetonitrile, (B) pyrrole-4-TSS-ZnSO(4)-acetonitrile, and (C) pyrrole-4-TSS-aniline-acetonitrile were investigated. In the case of system (A), effect of [4-TSS], [pyrrole], field intensity, and solvents H(2)O and CH(3)OH on morphology, fractal character, and growth kinetics was also studied. Fractal growth data were examined in detail. During studies on system (A), electric potential oscillations were observed and subjected to detailed study. The results indicate that fractal growth pattern and electric potential oscillations are inter-related. The mechanism of development of fractal growth, dendritic structure, and electric potential oscillations is discussed in terms of diffusion-limited aggregation and modified Diaz's mechanism, which explains the random movement of radical cations.

Gelrite microgels for sustained oral drug delivery-formulation and evaluation.

Gelrite is an ion-activated polymer prepared by partial acetylation of gellan gum, an exogeneous polysaccharide present in Pseudomonas elodea. Its unique cation-dependent gelling property at 33 degrees C has been exploited for the formulation of in situ gelling hydrogels for ophthalmic and oral drug delivery. Gelrite based oral formulations are known to sustain the drug levels at acidic pH due to the formation of 3D-lattice by cross-linking of uronic acid groups with cations. An extrusion method for formation of microspheres has been reported for Gelrite. The method cannot be successfully applied for encapsulation of hydrophilic moieties and has thus been modified in the present study. The microparticles prepared were optimized for various encapsulation variables such as particle size, shape, drug entrapment efficiency and in vitro drug release. A maximum of 41.87 +/- 0.2 % drug loading was obtained for the improved method. The drug release was found to be sustained in acidic medium (50% in SGF pH 1.2) for a period of 4 hours while burst release was observed in SIF pH 7.4. The work thus, presents a simplified microencapsulation method for hydrophilic drugs with higher entrapment efficiency for Gelrite, taking rifampicin as the model drug.

Interstitial ectopic pregnancy: A rare and difficult clinicosonographic diagnosis.

Ectopic pregnancy in the interstitial part of the fallopian tube is a rare event. This condition presents a challenge for clinical as well as radiological diagnosis. Although routine two-dimensional ultrasound can be suggestive, three-dimensional ultrasound is highly accurate in diagnosis. Hence, the authors report a rare case of interstitial ectopic pregnancy diagnosed preoperatively by three-dimensional ultrasound and managed laparoscopically.

Mediastinal pseudocysts in chronic pancreatitis with spontaneous resolution.

A 39 year old male, chronic alcoholic for 12 years, presented with recurrent abdominal pain for last 3 years. He was admitted in our hospital with history of breathlessness, chest pain and abdominal pain for last 20 days. On investigation he had raised total leukocyte count with elevated serum amylase and lipase. Chest radiograph showed mediastinal widening and ultrasound of abdomen revealed chronic pancreatitis with peripancreatic pseudocysts. CT scan revealed extensive phlegmonous collections with cyst formation in the mediastinum which extended from the level of thoracic inlet to below the level of the diaphragm. There were in addition multiple pancreatic and lesser sac pseudocysts. Patient was stable and was hence closely observed on conservative treatment with complete abstinence from alcohol. We performed no surgical, endoscopic or radiological interventions. A repeat CT performed after 14 weeks showed almost complete resolution of the mediastinal pseudocyst. Overall adequate conservative management and timely imaging follow-up before planning any intervention helped us to see that there can be spontaneous resolution of mediastinal pseudocysts.

Alginate microspheres of isoniazid for oral sustained drug delivery.

In the present study, spherical microspheres able to prolong the release of INH were produced by a modified emulsification method, using sodium alginate as the hydrophilic carrier. The shape and surface characteristics were determined by scanning electron microscopy using gold sputter technique. Particle sizes of both placebo and drug-loaded formulations were measured by SEM and the particle size distribution was determined by an optical microscope. The physical state of the drug in the formulation was determined by differential scanning calorimetry (DSC). The release profiles of INH from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of microspheres on oral administration and the extent of transit through the gastrointestinal tract (GIT). The microspheres had a smoother surface and were found to be discreet and spherical in shape. The particles were heterogeneous with the maximum particles of an average size of 3.719mum. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate microspheres were found to possess good bioadhesion (72.25+/-1.015%). The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4h and were detectable in the intestine 24h post-oral administration, although the percent radioactivity had significantly decreased (t(1/2) of (99m)Tc=4-5h). Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of INH was released in SGF pH 1.2 in 6h and 71.25% in SIF pH 7.4 in 30h. No significant drug-polymer interactions were observed in FT-IR studies. Dissolution and gamma-scintigraphy studies have shown promising results proving the utility of the formulation for enteric drug delivery.

Dynamic instability at liquid/vapor interface far from equilibrium.

Attempt has been made to elucidate the mechanism of electric potential oscillations at oil-aqueous solution interface involving adsorption at oil-vapor interface on a semi-theoretical basis. The mechanism stipulates adsorption of ammonia, amines and pheromones at the liquid-vapor interface followed by transfer of ions through membrane-aqueous solution interface and subsequent interaction of ammonium (amine) ions and carbocations from pheromones with diffusing halide ions from the bulk. Relationship of the above mechanism with sensing mechanism of smell by olfactory nerves has also been pointed out.