Absorption rate governs cell transduction in dry macroporous scaffolds.

Developing the next generation of cellular therapies will depend on fast, versatile, and efficient cellular reprogramming. Novel biomaterials will play a central role in this process by providing scaffolding and bioactive signals that shape cell fate and function. Previously, our lab reported that dry macroporous alginate scaffolds mediate retroviral transduction of primary T cells with efficiencies that rival the gold-standard clinical spinoculation procedures, which involve centrifugation on Retronectin-coated plates. This scaffold transduction required the scaffolds to be both macroporous and dry. Transduction by dry, macroporous scaffolds, termed "Drydux transduction," provides a fast and inexpensive method for transducing cells for cellular therapy, including for the production of CAR T cells. In this study, we investigate the mechanism of action by which Drydux transduction works through exploring the impact of pore size, stiffness, viral concentration, and absorption speed on transduction efficiency. We report that Drydux scaffolds with macropores ranging from 50-230 µm and with Young's moduli ranging from 25-620 kPa all effectively transduce primary T cells, suggesting that these parameters are not central to the mechanism of action, but also demonstrating that Drydux scaffolds can be tuned without losing functionality. Increasing viral concentrations led to significantly higher transduction efficiencies, demonstrating that increased cell-virus interaction is necessary for optimal transduction. Finally, we discovered that the rate with which the cell-virus solution is absorbed into the scaffold is closely correlated to viral transduction efficiency, with faster absorption producing significantly higher transduction. A computational model of liquid flow through porous media validates this finding by showing that increased fluid flow substantially increases collisions between virus particles and cells in a porous scaffold. Taken together, we conclude that the rate of liquid flow through the scaffolds, rather than pore size or stiffness, serves as a central regulator for efficient Drydux transduction.

Correlation of mortality with Pro-BNP and precipitating factors of acute heart failure in patients presenting to a medical emergency of tertiary care hospital: an observational study from north India.

OBJECTIVE: Acute heart failure is a syndrome defined as the new onset de novo heart failure or worsening [acutely decompensated heart failure (ADHF)] leading to symptoms and signs of HF, mostly related to systemic congestion as based on the European Society of Cardiology (ESC) definition. India has a huge burden of heart failure patients. Several factors have been identified as precipitating acute HF hospitalizations. These include myocardial ischemia, no adherence to medications, arrhythmias, infection, uncontrolled hypertension (HTN), anemia, renal impairment, and diet. However, there is a dearth of studies assessing their effect on mortality in patients admitted with acute heart failure. Many previous studies have shown that BNP and NT-pro-BNP are independent predictors of mortality and other cardiac outcomes in patients with heart failure (HF) and ADHF. However, no studies have provided any clear direction with respect to the critical cut-off values that suggest high mortality. Comprehensive knowledge of the correlation of Pro-BNP and precipitating factors of heart failure with mortality can help in prognostication and clinical management of AHF patients. PATIENTS AND METHODS: This was a prospective observational cross-sectional study conducted in the Emergency Department of the Postgraduate Institute of Medical Education and Research, Chandigarh which is a teaching and research hospital located in North India. Patients were enrolled from 1st August 2021 to 28th February 2022. Patients who met inclusion criteria were enrolled; they were followed for 5 days. After 5 days outcomes were recorded. Various precipitating factors for hospitalization were identified and their clinical impact on mortality was noted. Pro-BNP values were obtained at admission and their correlation with mortality and patient outcome after 5 days was noted. Values of Pro-BNP were compared among those who survived after 5 days vs. those who had fatal outcomes. RESULTS: The most common precipitating factor for AHF was poor medical compliance which did not affect mortality. It was followed by sepsis which significantly increases mortality in patients of AHF. ACS was also an important precipitating factor for AHF, though it had no effect on mortality. The mortality in the group of patients with very high Pro-BNP levels ≥ 2000 pg/ml was significantly higher than in the group of patients who had moderately elevated Pro-BNP < 2000 pg/ml. The median value of Pro-BNP was significantly higher in patients who had fatal outcomes [3670 (IQR- 2745 to 3980)] as compared to patients who survived after 5 days of hospitalization [1340 (IQR- 987 to 1670)]. CONCLUSIONS: Poor compliance with medications and sepsis are the most common precipitating factors for acute heart failure in north Indian patients. Sepsis as a precipitating factor is a significant risk factor for in-hospital mortality in acute heart failure patients presenting to the emergency department. Pro-BNP values above 2000 pg/ml in patients with acute heart failure requiring emergency admission are associated with a poor prognosis.

Topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries: a systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries among 1- to 16-year-old children. METHODS: PubMed, EbscoHost, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for randomised controlled trials. The trials should have assessed the caries-preventive effectiveness of topical fluoride-antibacterial agent (Povidone Iodine/Chlorhexidine/Xylitol/Triclosan/Cetylpyridinium Chloride) combined therapy versus topical fluoride monotherapy among children. Out of 3475 records that were screened, full text of 41 articles was assessed for potential inclusion. Sixteen trials that fulfilled the eligibility criteria were subjected to qualitative synthesis. The risk of bias was assessed using the Cochrane Collaboration's tool. Continuous data from nine trials were pooled using Inverse Variance test in meta-analysis function of Review Manager (version 5.4). GRADE approach was used to analyse the certainty of evidence. Statistical heterogeneity was quantified using the I2 statistic. A p-value of < 0.05 was considered as statistically significant. RESULTS: With respect to the caries increment, combined therapy showed superior caries-preventive effectiveness than topical fluoride monotherapy [SMD - 0.12, 95% CI (- 0.2 to - 0.04), p = 0.004; (I2 = 20%, p = 0.29)]. No significant difference was noted between the two groups for the post-intervention salivary S mutans count [SMD - 0.11, 95% CI (- 0.33 to 0.1), p = 0.3; (I2 = 0%, p = 0.77)]. CONCLUSION: The pooled analysis indicates towards an added benefit of topical fluoride-antibacterial agent combined therapy over topical fluoride monotherapy in preventing dental caries incidence among children. However, the results may be interpreted with caution since the evidence generated is of low certainty and is driven by two studies on Xylitol, thus it demands further good quality trials.

SYNTAX score in relation to intravascular ultrasound and near-infrared spectroscopy for the assessment of atherosclerotic burden in patients with coronary artery disease.

AIMS: The aim of this study was to examine the relationship between the anatomical SYNTAX score (SXscore), derived from all three coronary arteries, and coronary wall pathology measured by radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS) in a single non-culprit segment. METHODS AND RESULTS: In patients referred for coronary angiography (N=88) or PCI (N=592) for stable angina or acute coronary syndrome, the SYNTAX score calculator (www.syntaxscore.com) was used to determine the SXscore before PCI, if applicable. RF-IVUS and/or NIRS were performed in a non-stenotic 40 mm study segment following the clinically indicated angiography/PCI. After adjustment for multiple confounders, a higher SXscore was associated with higher segmental plaque volume in the study segment (2.21 mm3 per SXscore point, 95% CI: 0.92-3.50, p-value 0.001), as well as with higher volume of fibrous (0.93 mm3 per point) and fibro-fatty tissue (0.29 mm3 per point). A higher SXscore was also associated with a higher NIRS-derived lipid core burden index (LCBI) in the full study segment (1.35 units per SXscore point, 95% CI: 0.22-2.47, p-value 0.019). Importantly, SXscore correlated with the fatty/fibro-fatty and LCBI signals despite adjusting for plaque burden. CONCLUSIONS: In patients with CAD, higher SXscores are associated with higher atherosclerotic burden as assessed by RF-IVUS and NIRS in a single non-stenotic coronary artery segment.

Associations of 26 Circulating Inflammatory and Renal Biomarkers with Near-Infrared Spectroscopy and Long-term Cardiovascular Outcome in Patients Undergoing Coronary Angiography (ATHEROREMO-NIRS Substudy).

PURPOSE OF REVIEW: The purpose of this study was to investigate the association of 26 inflammatory biomarkers (acute phase proteins, cytokines, chemokines) and renal markers with coronary lipid core burden index (LCBI) assessed by near-infrared spectroscopy (NIRS) imaging, as well as the association of these biomarkers with long-term cardiovascular outcome. RECENT FINDINGS: NIRS-derived LCBI has recently been shown to be an independent predictor of major adverse cardiac events (MACE). However, studies on the association between circulating biomarkers and NIRS-derived characteristics have not yet been performed. Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris or acute coronary syndrome (ACS). NIRS of a non-culprit vessel was performed in a subset of 203 patients. In multivariable analyses, TNF-α tended to be associated with higher LCBI (beta 0.088 ln (pg/ml) increase per unit LCBI; 95% CI 0.000-0.177, p = 0.05) after adjustment for clinical characteristics. However, this association did not persist after Bonferroni correction (statistical threshold 0.0019). Major adverse cardiac events (MACE) were registered in 581 patients during a median follow-up time of 4.7 years (IQR: [4.2-5.6] years). After adjustment for clinical characteristics and Bonferroni correction, IL-8 (HR 1.60; 95% CI [1.18-2.17] per ln (pg/ml), p = 0.002) was borderline associated with MACE and significantly associated with all-cause mortality or ACS (HR 1.75; 95% CI [1.24-2.48] per ln (pg/ml), p = 0.0015). In conclusion, we found that IL-8 was independently associated with clinical outcome, but altogether, the multiplex panel we investigated here did not render a useful blood biomarker of high LCBI.

Serially measured circulating miR-22-3p is a biomarker for adverse clinical outcome in patients with chronic heart failure: The Bio-SHiFT study.

BACKGROUND: Several studies have suggested circulating microRNAs (miRs) are associated with heart failure, but these studies were small, and limited to single miR measurements. We examined 7 miRs which were previously linked to heart failure, and tested whether their temporal expression level predicts prognosis in a prospective cohort of chronic heart failure (CHF) patients. METHODS AND RESULTS: In 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3months, we measured 7miRs. The primary endpoint (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation and LVAD implantation. Associations between temporal miR patterns and the PE were investigated by joint modelling, which combines mixed models with Cox regression. Mean age was 67±13years, 72% were men and 27% NYHA classes III-IV. We obtained 873 blood samples (median 3 [IQR 2-5] per patient). The PE was reached in 41 patients (16%) during a median follow-up of 0.9 [0.6-1.4] years. The temporal pattern of miR-22-3p was independently associated with the PE (HR [95% CI] per doubling of level: 0.64 [0.47-0.77]). The instantaneous change in level (slope of the temporal miR pattern) of miR-22-3p was also independently associated with the PE (HR [95% CI] per doubling of slope: 0.33 [0.20-0.51]). These associations remained statistically significant after adjustment for temporal patterns of NT-proBNP, Troponin T and CRP. CONCLUSIONS: The temporal pattern of circulating miR-22-3p contains important prognostic and independent information in CHF patients. This concept warrants further investigation in larger series with extended follow-up.

Prevalence and Mophometry of Os Peroneum amongst Central Indians.

INTRODUCTION: Os Peroneum is round or oval shaped sesamoid within the substance of the Peroneus longus tendon as it plays on the Cuboid bone. MATERIALS AND METHODS: Thirty six embalmed cadavers were dissected bilaterally. Lateral part of foot and sole was dissected to expose Peroneus longus tendon and Os Peroneum. Measurements of Os Peroneum and articular surfaces of cuboid (calcaneum) were taken by the Digital Vernier Caliper. Histological and Radiological Examinations of Os Peroneum were also done. OBSERVATION: A flattened oval enlargement i.e. Os Peroneum was found in all the tendons examined. The deep surface of Os Peroneum (i.e. articular surface) was concave, smooth and shiny; sometimes divided into two parts. There was a well defined convex articular facet on the Cuboid at the proximal end of the peroneal sulcus, which sometimes extended proximally on to the Calcaneum forming a synovial joint. RESULTS: Average length of Os Peroneum was found to be 13.35 mm (Right - 13.35 mm, Left - 13.35 mm). Average breadth of Os Peroneum was 8.96 mm (Right - 8.87 mm, Left - 9.05 mm). Average thickness of Os Peroneum was 4.11 mm (Right - 4.13 mm, Left - 4.10 mm). Incidence of double articular facets on cuboid and Calcaneum was more on the right side (25.80%) than the left (16.20%). CONCLUSION: Findings suggest that Os Peroneum is present at the site of angulations of Peroneus Longus tendon with attendant change in direction and the exposure to various stresses and strains leading to its thickening and formation of Os Peroneum.

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma.

BACKGROUND: Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. METHODS: To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. RESULTS: Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients. CONCLUSION: In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.

Association of angiotensin-converting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome.

The aim of the study was to study the distribution of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its association with steroid responsiveness in children with idiopathic nephrotic syndrome (INS). One hundred twenty-five children with INS were classified into two groups: steroid-sensitive nephrotic syndrome (SSNS: n = 90) and steroid-resistant nephrotic syndrome (SRNS: n=35). The control group consisted of 150 unrelated healthy children. Genomic DNA was extracted from peripheral leucocytes by the standard salting-out method. ACE genotyping was performed and ACE genotypes DD, ID, and II were compared between different groups. The frequency distribution of the DD genotype was significantly increased in children with INS compared to control subjects (P = 0.0012) while the difference was not significant (P = 0.071) between SSNS and control subjects. The frequency distribution of the DD genotype was significantly high in the SRNS group compared to control subjects (P < 0.0001). The distribution of the DD genotype was high in SRNS compared to SSNS group patients (P = 0.016). In conclusion, the presence of the DD genotype may predict risk for steroid resistance in childhood INS.

Origins of the coronary arteries and their significance.

OBJECTIVE: To describe the normal and variant anatomy of the coronary artery ostia in Indian subjects. INTRODUCTION: Anomalous coronary origins may cause potentially dangerous symptoms, and even sudden death during strenuous activity. A cadaveric study in an unsuspected population provides a basis for understanding the normal variants, which may facilitate determination of the prevalence of anomalies and evaluation of the value of screening for such anomalies. METHODS: One hundred and five heart specimens were dissected. The number of ostia and their positions within the respective sinuses were observed. Vertical and circumferential deviations of the ostia were observed. The heights of the cusps and the ostia from the bottom of the sinus were measured. RESULTS: No openings were present in the pulmonary artery or the non-coronary sinus. The number of openings in the aortic sinuses varied from 2-5 in the present series; multiple ostia were mostly seen in the anterior sinus. The majority of the ostia lay below the sinutubular ridge (89%) and at or above the level of the upper margin of the cusps (84%). Left ostial openings were mainly centrally located (80%), whereas the right coronary ostia were often shifted towards the right posterior aortic sinus (59%). DISCUSSION: The preferential location of the ostia was within the sinus and above the cusps, but below the sinutubular ridge. On occasion, normal variants like multiple ostia, vertical or circumferential shift in the position, and slit-like ostia may create confusion in interpreting the images and pose a difficulty during procedures like angiography, angioplasty, and coronary artery bypass grafting.

Internal architecture of calcaneus: correlations with mechanics and pathoanatomy of calcaneal fractures.

BACKGROUND: Available studies on internal architecture of the calcaneus are cursory and contradictory. Present study focused on elaborate descriptions of the different trabecular groups and their correlation with the fractures of this bone. METHOD: To study the internal architecture, 50 dry adult human calcanei were sectioned in various planes and grossly dissected. RESULTS: Six different groups (A-F) of lamellae were identified. Based on the observations of trabecular architecture, potential weak areas in this bone were identified. The predicted weak zones correlate well with the fracture lines described in the calcaneus and provide anatomical basis for their occurrence. CONCLUSIONS: This study underscores the major influence of the internal architecture of the calcaneus in predicting the fracture lines. The findings can be utilized to classify fractures of calcaneus, which has been a topic of ongoing debate. Knowledge of weak zones will aid clinicians to improve the techniques of internal fixation.

Origins of the coronary arteries and their significance

Objective: To describe the normal and variant anatomy of the coronary artery ostia in Indian subjects. Introduction: Anomalous coronary origins may cause potentially dangerous symptoms, and even sudden death during strenuous activity. A cadaveric study in an unsuspected population provides a basis for understanding the normal variants, which may facilitate determination of the prevalence of anomalies and evaluation of the value of screening for such anomalies. Methods: One hundred and five heart specimens were dissected. The number of ostia and their positions within the respective sinuses were observed. Vertical and circumferential deviations of the ostia were observed. The heights of the cusps and the ostia from the bottom of the sinus were measured. Results: No openings were present in the pulmonary artery or the non-coronary sinus. The number of openings in the aortic sinuses varied from 2-5 in the present series; multiple ostia were mostly seen in the anterior sinus. The majority of the ostia lay below the sinutubular ridge (89 percent) and at or above the level of the upper margin of the cusps (84 percent). Left ostial openings were mainly centrally located (80 percent), whereas the right coronary ostia were often shifted towards the right posterior aortic sinus (59 percent). Discussion: The preferential location of the ostia was within the sinus and above the cusps, but below the sinutubular ridge. On occasion, normal variants like multiple ostia, vertical or circumferential shift in the position, and slit-like ostia may create confusion in interpreting the images and pose a difficulty during procedures like angiography, angioplasty, and coronary artery bypass grafting.

Internal architecture of the talus.

BACKGROUND: Ideally, bone has the external shape and internal architecture best adapted to its function. The internal architecture of the talus should reflect its functional adaptations. The purpose of this study was to evaluate the orientation of lamellae to account for its role in transmission of various forces. METHOD: Twenty-five pairs of dry adult human tali were sectioned in various planes and dissected grossly to study the internal architecture of the talus. RESULTS: Two sets of lamellae were observed in the body of the talus. One set was descending from the posterior two-thirds of the lateral part of trochlear surface onto the posterior calcaneal facet of the talus. These lamellae were in the form of vertical perforated interconnected plates. The second set of trabeculae originated from medial part of trochlear surface and anterior third of the lateral part. The neck of the talus showed the continuity of sagittal plates extending from the body to the head, which was occupied by stacked curved plates extending from infero-medial to the supero-lateral part of the head. CONCLUSION: We identified two sets of lamellae which we believe reflect the lines of forces of weightbearing through the talus. CLINICAL RELEVANCE: These findings may help in better understanding of fracture lines in the talus,which could improve internal fixation techniques, and the design of talar prostheses.

Chemokine receptor 5 (CCR5) deletion polymorphism in North Indian patients with coronary artery disease.

BACKGROUND: Polymorphisms in genes coding for chemokine receptors, CCR2 and CCR5 have been studied as genetic markers of coronary artery disease (CAD). V64Ile polymorphism in CCR2 has been implicated in the manifestation of myocardial infarction in different populations, but data on association of the CCR5 deletion variant in etiology of CAD are conflicting. In the present study we tested genetic association between CCR5 Delta32 polymorphism and CAD among North Indians (Uttar Pradesh). METHODS: Two hundred angiographically proven patients with coronary artery disease and two hundred age, sex and ethnically matched controls were genotyped for CCR5 Delta32 polymorphism by polymerase chain reaction. Genotype/allele frequencies were compared in patients and controls using the chi-square test. RESULTS: The frequency of the heterozygote genotype in the population, including both patient and control group, was 3% and the frequency of the mutant allele Delta32 was 1.5%. CAD patients had a three times higher (4.6% vs. 1.5%) frequency of heterozygote genotype but the differences were statistically not significant. Association analysis did not achieve statistical significance, though odds ratio of 3.13 was observed for heterozygote genotype. CONCLUSIONS: The allele frequency of the CCR5 Delta32 polymorphism in CAD patients is 2.25% and 0.75% among controls but the differences were not significant. Overall this fits well with the pattern of CCR5 Delta32 allele frequency in Indian subcontinent where it varies from 1 to 3%. The heterozygote (+/ Delta32) genotype does not seem to have any protective role against development of CAD in this population. In fact, North Indian CAD had a higher frequency of CCR5 Delta32 allele suggesting a possible susceptibility trend (odds ratio 3.08, CI 0.83-11.46, chi-square 2.167, NS).

Uptake of invasive prenatal diagnostic tests in women after detection of soft markers for chromosomal abnormality on ultrasonographic evaluation.

OBJECTIVE: Use of soft ultrasonographic markers during routine prenatal ultrasonography (USG) may be used for the screening of aneuploidy in the low-risk population. The aim of this study was to evaluate the acceptance of an invasive test for prenatal diagnosis and to assess the role of various factors in the decision-making regarding an invasive test when confronted with risk for aneuploidy after a soft marker is detected on routine antenatal ultrasonogram. STUDY DESIGN: Women were referred for USG in our department by primary obstetricians for indications such as a previous child with a congenital malformation, genetic disorder, stillbirth or in women with recurrent spontaneous abortions. Some of the women were referred after prenatal detection of a soft marker on USG. They were screened for soft markers associated with chromosomal abnormality. They were counseled regarding the age-specific risk and the risk of aneuploidy after detection of a marker in comparison to the general population's risk of Down's syndrome. They were also counseled regarding the risk of a procedure-related abortion (0.5%) following an invasive procedure before their decision regarding the use of amniocentesis was made. RESULT: Twenty women out of 50 (40%) opted for amniocentesis. Except in one case of trisomy 21 in a fetus with short femur and humerus, all others had normal karyotype. The uptake of the test was comparable between primigravida (33%), women with poor obstetric history (46%) and women with at least one normal live child (45%). There was no statistical difference in the uptake of invasive test based on gestational age as well. Uptake of amniocentesis was higher (78%) in cases with nuchal thickening as compared to other markers (35%). CONCLUSION: Ultrasonographic detection of soft markers is associated with a high frequency of uptake for invasive prenatal testing. Increased nuchal thickening is associated with a higher acceptance of amniocentesis. Maternal age, gestational age or previous obstetric history were not associated with the decision to undergo amniocentesis.

Domain interaction in cyanobacterial phytochromes as a prerequisite for spectral integrity.

Two phytochromes, CphA and CphB, from the cyanobacterium Calothrix PCC7601, with similar size (768 and 766 amino acids) and domain structure, were investigated for the essential length of their protein moiety required to maintain the spectral integrity. Both proteins fold into PAS-, GAF-, PHY-, and Histidine-kinase (HK) domains. CphA binds a phycocyanobilin (PCB) chromophore at a "canonical" cysteine within the GAF domain, identically as in plant phytochromes. CphB binds biliverdin IXalpha at cysteine24, positioned in the N-terminal PAS domain. The C-terminally located HK and PHY domains, present in both proteins, were removed subsequently by introducing stop-codons at the corresponding DNA positions. The spectral properties of the resulting proteins were investigated. The full-length proteins absorb at (CphA) 663 and 707 nm (red-, far red-absorbing P (r) and P (fr) forms of phytochromes) and at (CphB) 704 and 750 nm. Removal of the HK domains had no effect on the absorbance maxima of the resulting PAS-GAF-PHY constructs (CphA: 663/707 nm, CphB: 704/750 nm, P (r)/P (fr), respectively). Further deletion of the "PHY" domains caused a blue-shift of the P (r) and P (fr) absorption of CphA (lambda (max): 658/698 nm) and increased the amount of unproperly folded apoprotein, seen by a reduced capability to bind the chromophore in photoconvertible manner. In CphB, however, it practically impaired the formation of P (fr), i.e., showing a very low oscillator strength absorption band, whereas the P (r) form remains unchanged (702 nm). This finding clearly indicates a different interaction between domains in the "typical", PCB binding and in the biliverdin-binding phytochromes, and demonstrates a loss of oscillator strength for the latter, most probably due to a strong conformational distortion of the chromophore in the CphB P (fr) form.

Monitoring vital signs in a bone marrow transplant unit: are they needed in the middle of the night?

Monitoring vital signs (VS) is a routine procedure in bone marrow transplant (BMT) units, but such monitoring can interfere with sleep. We hypothesized that middle of the night (MON) monitoring may not be needed in all patients. Charts of 20 consecutive patients who underwent BMT were reviewed for MON monitoring to determine the frequency with which monitoring resulted in a nursing intervention, call to the physician or change in treatment by the physician. Charts were also reviewed for day time events, which could predict the need for monitoring at night. MON monitoring was done on 457 of the 543 nights evaluated, 148 nursing interventions were performed during these 457 nights (32%) of which only 20 (4%) were the result of monitoring VS. In five instances, the nurse called the physician as a result of monitoring VS and in three of these five instances, the treatment was changed. The only day time event that was significantly associated was fever (P = 0.0002). There was also a trend for CNS events (P = 0.057) to be associated with MON intervention. Larger, prospective studies need to be done to accurately identify day time risk factors that can predict the need for night time monitoring.

VALETHEMATE BROMIDE AND CERVICAL DILATATION.

The importance of cervical dilatation in normal labour is well known & cervical dystocia is known to prolong labour adversely affecting fetomaternal well being. Valethemate bromide(Injection Epidosin) has been known to shorten the first stage of labour & several studies have proved the efficacy of this drug. Injection Epidosin was used on five hundred patients (250 Primigravida and 250 multiparas) having uncomplicated labour and its efficacy in shortening the first stage of labour was studied. This study proved that epidsosin could reduce first stage of labour in primigravidas as well as multiparas significantly without any major side effects and could be used safely under supervision of a nursing staff.