Atovaquone–Proguanil (Malarone): an Effective Treatment for Uncomplicated Plasmodium falciparum Malaria in Travelers from Denmark

Background Previous experience with unacceptable adverse effects with mefloquine as treatment for uncomplicated Plasmodium falciparum malaria prompted an evaluation of the effectiveness and side effects of atovaquone–proguanil (Malarone) in a hospital setting.
Methods Atovaquone–proguanil was given as standard treatment (1,000/400mgq.d. for 3 days) to 50 adults who had traveled in Africa and returned with uncomplicated Plasmodium falciparum malaria. Half of the treated patients were African and had lived outside Africa for varying periods of time; the other half were Danish-born persons without any previous immunity towards malaria.
Results All patients treated with Malarone were cured without complications. The mean fever clearance times differed among the groups and according to various degrees of prior exposure to malaria and ranged from 1.3 to 2.2 days. Adverse effects during treatment were mild, and were likely to be due to the malaria itself. Fourteen people who had acquired falciparum malaria in spite of taking proguanil–chloroquine prophylaxis were also cured uneventfully without recrudescence.
Conclusions Malarone appears to be an effective, safe and acceptable oral treatment for uncomplicated malaria.     

Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure–EEM relationships and kinetics revealed that the components extracted from EEM–PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM–PARAFAC methodology.

Drug quality and assurance changes with time under the influence of a variety of environmental factors, such as light, temperature, and moisture.     

Gingival recessions caused by Herpes Simplex Virus in a patient with COVID‐19 infection

Herpes Simplex Virus type 1 (HSV‐1) is a very common infection often localized in the mucocutaneous junction of the lip. Rarely, it could be detected also in periodontal tissues, associated with an elevated risk of periodontal disease progression and gingival recessions. Recently, HSV‐1 and numerous co‐infections have been reported in literature associated with the Coronavirus and subsequent COVID‐19 disease. This report illustrates a case of HSV‐1 in a patient with Covid‐19 infection, showing the presence of ulcers and vesicles on the gingival margin of maxillary teeth associated with soreness and pain. The histology highlighted the presence of intraepithelial cell ballooning, confirming the diagnosis of HSV‐1 infection.     

Vaginal birth after cesarean: do California hospital policies follow national guidelines?

OBJECTIVE: To review whether California hospitals are adhering to national practice guidelines with regard to vaginal birth after cesarean (VBAC). STUDY DESIGN: We performed a content analysis of the American College of Obstetricians and Gynecologists (ACOG) and American Association of Family Physicians published guidelines and identified 39 specific recommendations, which were categorized into the following 5 content areas: patient criteria, procedure, staff and resources, uterine rupture or other complications, and miscellaneous clinical issues. We evaluated individual hospital policies with regard to adherence to 34 recommendations made specifically by ACOG. RESULTS: Of the 225 surveyed hospitals, 167 (74%) allow VBAC, and 22% of these (36 of 167) provided VBAC protocols for review. Approximately 80% of protocols included < 50% of the ACOG items (median, 13.5; range, 3-27 items). The highest percent adherence was observed in the procedure and staff and resources categories, where over two thirds of study hospitals exhibited 75-100% adherence. One third of participating hospitals were less adherent (0-25%) in the categories of patient criteria, uterine rupture or other complications, and miscellaneous clinical issues. CONCLUSION: In a sample of written VBAC protocols, we found a wide range of adherence to ACOG recommendations, as evidenced by the number and type of items explicitly documented in the protocols.     

ENHANCEMENT OF THE OPSONIZING AND AGGLUTINATING POWERS OF ANTIPNEUMOCOCCUS SERUM BY SPECIFIC PRECIPITATING SERUM

1. No demonstrable antiopsonins are formed in rabbits following the intravenous injection of monovalent pneumococcus horse sera, Types I, II, and III. 2. The serum of rabbits injected with immune pneumococcus horse serum, Type I, II, or III, or with normal horse serum, when mixed in the proportion of 1:4 with Type I or Type II pneumococcus horse serum, can greatly augment, in vitro, the opsonization and agglutination of Type I and Type II pneumococci by the homologous immune horse sera. No similar effect is obtained with Type III serum and pneumococci. 3. The increase in opsonization and agglutination is dependent upon (a) specific sensitization of the pneumococci by the homologous immune serum and (b) the presence of the precipitating serum. In the absence of sensitization, as when a heterologous or normal horse serum is employed, opsonization and agglutination do not occur, even though a precipitating mixture is provided. The substitution of normal rabbit serum for the precipitating rabbit serum gives opsonization and agglutination in dilutions slightly higher than are effected with salt solution only, due possibly to the more favorable medium created for the leucocytes by the addition of 25 per cent of whole rabbit serum. 4. Different methods of combining the immune horse serum, precipitating rabbit serum, and pneumococci yield very similar results, preliminary sensitization of the bacteria before precipitation, or precipitation in the rabbit-horse serum mixture before the addition of the pneumococci for sensitization causing little if any difference in result from that obtained when immune horse serum, precipitating rabbit serum, and pneumococci are all mixed and incubated together. 5. This increased opsonization in the test-tube does not seem to be paralleled by increased protective power, or at any rate such protection is not readily demonstrated.     

Development of the Japanese version of the Pediatric Quality of Life Inventory™ Brain Tumor Module

Background

The Pediatric Quality of Life Inventory? (PedsQL?) is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL? Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL? Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents.

Methods

Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children.

Results

Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70) except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95). Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents). Evaluation of known-groups validity confirmed that the Cognitive Problems scale was sensitive for developmental impairment, the Movement and Balance scale for infratentorial tumors or paresis, and the Nausea scale for a patient currently undergoing chemotherapy. Convergent and discriminant validity with the PedsQL? Generic Core Scales and State-Trait Anxiety Inventory for children were acceptable.

Conclusions

The Japanese version of the PedsQL? Brain Tumor Module is suitable for assessing health-related quality of life in children with brain tumors in clinical trials and research studies.     

Effects of preshock experience on enhancement of rat brain noradrenaline turnover induced by psychological stress

The present study examined alterations of brain noradrenaline (NA) turnover as a function of preshock and psychological stress treatments, by measuring contents of NA metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Psychological stress induced by exposing to the sight, sound and odor of other rats being shocked produced higher levels of MHPG-SO4 in the hypothalamus, amygdala and locus coeruleus (LC) region, as well as higher levels of plasma corticosterone. Preshock experienced rats also showed marked increases of MHPG-SO4 levels in the same regions described above and elevated plasma corticosterone levels when placed but not shocked in the same environment in which the rats had previously received shocks. The effects of psychological stress on brain NA turnover were affected by the animal's shock history preferentially in the hypothalamus and amygdala. These results suggest that: a purely psychological stressor caused acutely enhanced NA turnover in specific brain regions; regional NA activity appeared to be reinstated simply by reexposure to the environment previously associated with shock; preshock experience further intensified the enhancement of amygdaloid NA turnover evoked by psychological stress. An additional experiment, studying the aftereffects of preshock experience, clearly showed that these findings result from sensitization or conditioning to the environment previously paired with shock, and not merely from the aftereffects of the shock per se.     

Role of SCOX in determination of Drosophila melanogaster lifespan

In man, COX (cytochrome c oxidase) deficiency is reported to be related to mutation of the SCO2 (synthesis of cytochrome c oxidase 2) gene, which encodes one of the copper-donor chaperones involved in the assembly of mitochondrial cytochrome c oxidase. Such COX deficiency due to the genetic condition leads to heart disease and the Leigh syndrome and is frequently fatal in childhood. Synthesis of cytochrome c oxidase X (SCOX) is a Drosophila orthologue of human SCO2. Here, we generated SCOX-knockdown flies and the full length SCOX transgenic flies to investigate the in vivo roles of SCOX. Our results demonstrated knockdown of SCOX gene in all cells and tissues to be associated with lethality at larval or pupal stages and this correlated with a decrease in ATP level. In contrast, the full length SCOX transgenic flies showed a longer lifespan than wild type flies and control flies carrying Act5C-GAL4 alone and this correlated with an increase in ATP level. Finally, when cultured on paraquat-added medium, full length SCOX transgenic flies also exhibited an elongated lifespan. Therefore, we hypothesized that SCOX plays an important role in ATP production and consumption, which helps to prevent production of mitochondrial reactive oxygen species and/or impairment of mitochondrial activity under oxidative stress.