A quest for cytocompatible metal organic frameworks in non-viral gene therapy: Relevance of zeolitic imidazolate framework-8.

Metal-organic frameworks (MOFs) are an emerging group of nanomaterials for successful biomedical applications in gene therapy. The most commonly biocompatible MOFs are zinc-based ZIFs, zirconium-based UiOs, and iron-based MILs. However, despite increasing applications, a comparative study to underscore the critical factors for determining effective gene delivery by such MOFs is lacking. Herein, we evaluate the potential of UiO-66 and MIL-88B and ZIF-8 for gene therapeutics delivery; revealing the comparative importance of ZIF-8. Cytotoxicity assays proved insufficient for selecting the ideal gene delivery MOF vehicle. Synthesis conditions such as ability of the MOF scaffold to envelop the gene during in-situ synthesis, post-treatment such as washing, and gene loading efficiency proved to be the critical factors in determining the favourable MOF from the material selection perspective. Rapid in-situ synthesis under physiological conditions, successful gene loading, and low concentration requirements favour ZIF MOFs as gene delivery vehicles. Impact on cellular physiology, metabolism, and architecture revealed neutrality of the delivery system; and relative effects on pro-inflammatory and anti-inflammatory cytokines suggest immunomodulatory impact.

Standards of care provided by early pregnancy assessment units (EPAU): a UK-wide survey.

Standards of services provided by the EPAUs across the UK vary from one unit to another. The aim of this purposive sampling self-administered survey was to assess these standards against a benchmark set by the Royal College of Obstetricians and Gynaecologists (RCOG). These standards were set out in a report by a RCOG working party (2008). Out of 181 units contacted in this survey, 140 units responded. We looked at the setup of the EPAU, services offered, accessibility and protocols for management of miscarriage and ectopic pregnancy. The survey shows that there is a considerable variation in the management protocols and the quality of services offered by the EPAUs in the UK. Many units do not meet the standards set by the RCOG.

Paraneoplastic polymyositis presenting as a clinically occult breast cancer.

Paraneoplastic syndrome affects less than 1% of cancer patients. Diagnosis of paraneoplastic syndrome with neurological presentation requires screening for an underlying malignancy, including a complete history, physical examination and imaging studies. Treatment often results in symptom stability, rather than improvement. Paraneoplastic polymyositis can precede or instantaneously occur at diagnosis or treatment of a primary tumour, while neurological symptoms can persist even following cancer treatment. We report a rare case of metaplastic breast carcinoma with an unusual presentation of paraneoplastic polymyositis.

Role of the stability of charge ordering in exchange bias effect in doped manganites.

In this work we have carried out an elaborate study on the magnetic properties and investigated the exchange bias phenomena of some charge-ordered (CO) manganites. The detailed study of Sm1-x Ca x MnO3 (x = 0.5, 0.55, 0.6, 0.65, 0.7) compounds shows that Sm0.4Ca0.6MnO3, which is the most robust charge ordered material studied here, shows significantly large exchange bias field (HE) as compared to the other compounds. Our experimental results and analysis indicate that TCO, which reflects the stability of the charge-ordered state, is one of the key parameters for the exchange bias effect. Similar behaviour is found in other rare-earth analogues, viz., La1-x Ca x MnO3 and Pr1-x Ca x MnO3 compounds as well. We also found that with increasing stability of CO states in Sm1-x Ca x MnO3 compounds, HE enhances due to increase in number and reduction in size of ferromagnetic clusters.

Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale.

The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La(1-x)Ca(x)MnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology.

Absence of low energy magnetic spin-fluctuations in isovalently and aliovalently doped LaCo2B2 superconducting compounds.

Magnetization, resistivity and (11)B, (59)Co NMR measurements have been performed on the Pauli paramagnet [Formula: see text], and the superconductors [Formula: see text] ([Formula: see text] K) and [Formula: see text] ([Formula: see text] K). The site selective NMR experiment reveals the multiband nature of the Fermi surface in these systems. The temperature independent Knight shift and 1/T 1 T clearly indicate the absence of correlated low energy magnetic spin-fluctuations in the normal state, which is in contrast to other Fe-based pnictides. The density of states (DOS) of Co 3d electrons has been enhanced in superconducting [Formula: see text] and [Formula: see text] with respect to the non superconducting reference compound [Formula: see text]. The occurrence of superconductivity is related to the DOS enhancement.

The spindle checkpoint of the yeast Saccharomyces cerevisiae requires kinetochore function and maps to the CBF3 domain.

We have measured the activity of the spindle checkpoint in null mutants lacking kinetochore activity in the yeast Saccharomyces cerevisiae. We constructed deletion mutants for nonessential genes by one-step gene replacements. We constructed heterozygous deletions of one copy of essential genes in diploid cells and purified spores containing the deletion allele. In addition, we made gene fusions for three essential genes to target the encoded proteins for proteolysis (degron alleles). We determined that Ndc10p, Ctf13p, and Cep3p are required for checkpoint activity. In contrast, cells lacking Cbf1p, Ctf19p, Mcm21p, Slk19p, Cse4p, Mif2p, Mck1p, and Kar3p are checkpoint proficient. We conclude that the kinetochore plays a critical role in checkpoint signaling in S. cerevisiae. Spindle checkpoint activity maps to a discreet domain within the kinetochore and depends on the CBF3 protein complex.

Hematopoietic regulation mediated by interactions among the neurokinins and cytokines.

This review summarizes the current data regarding the mechanisms by which two mammalian neurokinins (tachykinins), substance P (SP) and neurokinin-A (NK-A) are involved in hematopoiesis. SP and NK-A are derived from the preprotachykinin-I (PPT-I) gene which can be induced by cytokines and neurotrophic factors. In the bone marrow (BM), nerve fibers and stroma are potential sources for the PPT-I gene products. SP and NK-A interact with either of three cloned receptors, neurokinin-1 (NK-1), NK-2 or NK-3, although SP and NK-A exhibit binding preferences for NK-1 and NK-2 respectively. Through specific receptors, SP and NK-A exert dichotomous hematopoietic effects mediated mostly by the BM stroma. SP enhances the proliferation of primitive BM stem cells and progenitors and these effects correlate with the induction of stimulatory hematopoietic growth factors. NK-A appears to be protective to stem cells through the induction of TGF-beta. Proliferation of myeloid progenitors is inhibited by NK-A, effects which correlate with the induction of two suppressive factors, TGF-beta and MIP-1alpha. Stimulation of NK-2 leads to partial blunting of the enhanced stimulatory effects mediated by NK-1. Furthermore, stimulatory hematopoietic cytokines upregulate NK-1 expression and downregulate the constitutively expressed NK-2 in BM stroma. Together, the experimental evidence suggests that NK-A-NK-2 interactions could be a feedback to hematopoietic stimulation. Expression of NK-1 and NK-2 in CD34+ cell lines and also, the presence of SP binding sites on primary CD34+ cells suggest that the neurokinins could be interacting directly with BM progenitors and stem cells. In BM stroma, cytokines and neurokinins regulate the expression of each other and also, their respective receptors. In summary, the current literature pertaining to hematopoietic regulation indicates the involvement of a complex network that includes, but not exclusive of the cytokines and neurokinins. The current models that pertain to stem cell proliferation and differentiation should therefore add neuropeptides to the list of hematopoietic modulators.

Generation and characterization of a polyclonal antipeptide antibody to human glycodelin.

OBJECTIVE: To develop and characterize an antiglycodelin antibody using a 15-amino acid synthetic peptide as antigen, derived from the sequence of human glycodelin. DESIGN: We have developed a chicken antiglycodelin-derived peptide antibody and have characterized the antibody with the use of endometrial and ovarian cell lines. The antibody was also tested for its ability to detect glycodelin by ELISA assay, immunocytochemistry, and by Western blot. SETTING: Various cell lines, cell culture medium, and amniotic fluid were used in the experiments. PATIENT(S): Amniotic fluid was collected from pregnant patients in their first trimester of pregnancy. INTERVENTION(S): No intervention. MAIN OUTCOME MEASURE(S): Detection of glycodelin. RESULT(S): The cell lines RL95-2 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), HeLa (human cervical epitheloid carcinoma cells), and EM42-D (human endometrial epithelial cells) reacted with the antibody, indicating the presence of glycodelin. A specific 45-kd protein representing glycodelin was detected by Western blot in the amniotic fluid. CONCLUSION(S): Antipeptide antibodies can be successfully used to detect and quantify the presence of glycodelin in cells and fluids.

Effects of cyproterone acetate on reproductive functions in normal human males.

PIP: The effects of cyproterone acetate (CA) on reproductive functions in normal human males were studied. 6 volunteers received 5 or 10 mg CA over a 20-week period. The treatment caused a gradual decrease in the number of spermatozoa and their motility, and an increase in the percentage of nonmotile, abnormal, and immature sperms. There was also a marked inhibition of sperm transport of motile sperm through cervical mucus, as determined by Kremer's test. Semen levels of acid phosphatase, sialic acid, and glycerylphosphorylcholine progressively decreased, though semen levels of fructose were not markedly altered. There were no marked changes in levels of SGOT, SGPT, serum alkaline phosphatase, blood urea, and hematocrit values. The possible mode of action of CA and its potential as a male contraceptive agent are discussed.^ieng

Effects of intravasal nylon thread on the spermatozoa & reproductive organs in rats.

PIP: An investigation was undertaken in rats to study the effects of intr avasal thread (IVT) on the spermatozoa in the vas deferens and reproduct ive organs at various intervals after IVT insertion. The quantity of sperm was slightly reduced and motility was greatly reduced in the distal portion of the vas. The percentage of head and tail separation of sperm in the distal vas decreased with time. The quantity of sperm always remained the same in the cauda epididymis although the percentage of motile sperm decreased at 1 and 6 months, but not at 9 months, after IVT insertion. Following IVT insertion there was insignificant change in the weight of the testis, epididymis, ventral prostate, and seminal vesicles and alkaline phosphatase activity in the ventral prostate. Although cause and significance of these findings are unclear, the sialic level in the epididymis was significantly reduced in all groups bearing IVT. The presence of IVT apparently causes a change to occur in the epididymis, but it is unknown whether this affects sperm maturation.^ieng

Surgical sterilization in a hospital.

PIP: The influence of a family planning promotion effort on the number of tubectomies and vasectomies performed at a New Delhi hospital is evaluated. The program, which was conducted during 1964-1967, involved: 1) training and orientation courses for physicians, nurses, and ministerial staff in surgical sterilization and other family planning methods; 2) the education of all hospital patients and visitors in family planning; and 3) easy access and availability of sterilization services and other family planning methods. The number of tubectomies and vasectomies performed remained fairly constant until 1966, when the incidence increased about 2 1/2 times in 1 year. Vasectomy reached a plateau in 1967-1968, and then declined almost as rapidly as it rose to preprogram levels. Tubectomy, however, continued to increase until the incidence in 1972 was almost 10 times that of 1964. The decrease in the incidence of vasectomy may be attributable to changes in personnel and the discontinuation of the intensive education program. Postpartum family planning education, and the insistence on sterilization of abortion seekers with 3 or more children were largely responsible for the increase in tubectomy.^ieng

Disappearance of spermatozoa from semen after vasectomy.

PIP: Of 1200 individuals vasectomized, only 450 later had their semen tested for spermatozoa. Information on the number of seminal ejaculations after the operation was obtained from 254 persons. The semen analysis was done only once in 317 cases, twice in 97 cases, and 3 or more times in 36 cases. 375 of the 450 cases were sperm-free when the last test was done. Only 23 (5%) had spermatozoa 3 months after the operation. 3 (.7%) of these had 15-40 million spermatozoa/ml of semen with more than 60% motility 6 months after vasectomy. These patients required reoperation. Result indicated that contraceptive precautions are often needed for 3 months, of after 15 ejaculations, following the vasectomy. Semen tests should be done to confirm absence of spermatozoa.^ieng

Cholesterol and ascorbic acid in semen under varied clinical conditions.

PIP: Fresh semen samples were collected from a total of 269 individuals attending the Family Welfare Planning Clinic. 29 had azoospermia following vasectomy, 12 had azoospermia due to spermatogenic defect, and the remainder had varying grades of sperm density and motility. Physical and morphological evaluations of the semen samples were made. Ascorbic acid was estimated in whole semen by the method of Roe an Kuether. Total cholesterol in plasma was determined. The total cholesterol concentration showed a gradual decline in the group with sperm count of 1-20 million/ml to the lowest level in the group with a count of 61-80 million. It then increased progressively up to the counts of 101-120 million/ml. Ascorbic acid concentration was significantly higher in patients with azoospermia due to defective spermatogenesis. The azoospermic specimens of vasectomized individuals contained significantly higher level of ascorbic acid than in dysspermatogenic azoospermia. The percentages of motile sperm in samples were unrelated to either cholesterol or ascorbic acid concentrations.^ieng

Perception about AIDS among residents of a Calcutta slum.

A study was carried out in a slum area of South Calcutta to assess the impact of the current mass education programme against AIDS. Two hundred and six residents, mainly of lower middle class, aged 18-60 years of both sexes were selected at random. They were interviewed to know their perception and sources of information about AIDS. Two-third of them had their own TV and radio, which they watched/heard for about three and half hours each day. Another 28% watched TV outside for about one and half hours a day. About 46% were daily readers and 20% occasional readers of newspapers. Fifty nine percent knew about persons vulnerable to get AIDS, but most of them associated it to promiscuity only. Avoiding it was the main means known to them for preventing AIDS. The role of condom in it was known to only 2.5% residents. The source of their knowledge was mainly TV, either alone or with other mass media (67%). Such knowledge was related to higher education. To make perception about AIDS more effective, it is suggested that local health and voluntary agencies should involve the community in the AIDS education programme along with the back-up of mass media. An apex agency solely responsible for AIDS education should be set up for each big city to co-ordinate the activities of local agencies.

PIP: 206 mainly poor and lower middle-class residents of the Chetla slum of South Calcutta were interviewed with regard to their perceptions and sources of information about AIDS. The goal was to assess the impact of the current mass education program against AIDS. One member was randomly selected from each of 206 families to participate in the study. Respondents were aged 16-80 years, of mean age 35-42 years, 43.7% male, 80% married, 19% illiterate, and 94% Hindu. 66% had their own television and radio which they watched/heard for approximately 3.5 hours daily. Another 28% watched television outside for approximately 1.5 hours each day. Approximately 46% and 20% were daily and occasional newspaper readers, respectively. 59% knew about people vulnerable to contracting AIDS, but most associated HIV risk only with promiscuity and prostitution. Avoiding such behavior was deemed to be the best way to avoid contracting HIV. Only 2.5% knew that condom use can protect against HIV infection. The source of that knowledge was mainly television, either alone or with other mass media. Such knowledge was related to higher education. The authors suggest that local health and voluntary agencies involve the community in the AIDS education program, backed up by the mass media. An agency solely responsible for AIDS education should be established in each major city to coordinate local agency activities.

Evidence of a structural phase transition in superconducting SmFeAsO(1-x)F(x) from 19F NMR.

We report resistivity, magnetization and (19)F NMR results in a polycrystalline sample of SmFeAsO(0.86)F(0.14). The resistivity and magnetization data show a sharp drop at 48 K indicating a superconducting transition. The nuclear spin-lattice rate (1/T(1)) and spin-spin relaxation rate (1/T(2)) clearly show the existence of a structural phase transition near 163 K in the sample, which also undergoes a superconducting transition. This finding creates interest in exploring whether this is unique for Sm based systems or is also present in other rare-earth based 1111 superconductors.