Multilocus species-delimitation in the Xerotyphlops vermicularis (Reptilia: Typhlopidae) species complex.

Scolecophidia (worm snakes) are a vertebrate group with high ecomorphological conservatism due to their burrowing lifestyle. The Eurasian or Greek blindsnake Xerotyphlops vermicularis is their only European representative, a species-complex with an old diversification history. However, its systematics and taxonomy has remained untouched. Here, we extend previous work that relied heavily on mitochondrial markers, following a multi-locus approach and applying several species-delimitation methods, including a Bayesian coalescence-based approach (STACEY). Four "species" delimitation analyses based on the mtDNA (ABGD, bGMYC, mPTP, parsimony networks) returned 14, 11, 9 and 10 clusters, respectively. By mitotyping twice as many specimens as before, we have a complete picture of each cluster's distribution. With the exception of the highly-divergent Levantine lineage, the three independent nuclear markers did not help with phylogenetic resolution, as demonstrated in haplotype networks, concatenated and species-trees, a result of incomplete lineage sorting. The prevailing model from the coalescence-based species-delimitation identified two species: the lineage from the Levant and all others. We formally recognize them as distinct species and resurrect Xerotyphlops syriacus (Jan, 1864) to include the Levantine blindsnakes. Finally, X. vermicularis and X. syriacus may represent species-complexes themselves, since they include high levels of cryptic diversity.

Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials.

BACKGROUND: Targeting immune checkpoints is a novel approach in cancer therapy. This strategy may trigger immune related adverse events (irAE). We hypothesize that the incidence of irAE will be greater in patients receiving immune checkpoint inhibitors (ICI) targeting only immune cells compared to those that also target tumor cells (PD-L1). In addition, we compared the specific irAE profile and overall response rate (ORR) for each ICI by target(s). MATERIALS AND METHODS: We reviewed all ICI cancer clinical trials (90; 174 arms) that reported irAE and were published through MEDLINE. 114 arms from 73 trials were eligible for this meta-analysis (including 11,328 patients). We collected and compared arm-specific data including ICI target, number of patients with irAE of any grade, grade 3+ and grade 5, specific irAE, and ORR. The R package "meta" was used to conduct a meta-analysis to calculate and compare the percentage of patients with irAE and ORR. RESULTS: The incidence (% of patients) of any grade irAE per ICI target was reported for 40 arms (3418 patients) treated with ICI. Most arms (80%) and patients (53%) studied were on phase 1/2 clinical trials. Patients were treated for solid malignancy on 39 arms (97%), mainly melanoma (40%). Two arms included ICI combinations. The incidence of any grade irAE was higher in patients who received ICI targeting CTLA-4 (53.8%) than PD-1 (26.5%) and PD-L1 ICI (17.1%) (P<0.001). Comparative specific irAE rates were calculated for each ICI target. CONCLUSIONS: Our systematic review supported our mechanistic-driven hypothesis. We encourage investigators to report the incidence of irAE in future ICI combination trials.

Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.

BACKGROUND AND OBJECTIVE: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. PATIENTS AND METHODS: Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. RESULTS: No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "+/- TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. CONCLUSION: These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP.

[Sandflies of Lebanon: faunistic inventory]. / Les phlébotomes du Liban. Inventaire faunistique.

An entomological study was made in order to complete the epidemiological data on leishmaniasis in Lebanon. 19 species of sandflies (13 of the genus Phlebotomus and six of the genus Sergentomyia) were found. The list includes a recently described species of the Synphlebotomus subgenus (P. saltiae) and eight other species mentioned for the first time in Lebanon: P. neglectus, P. brevis, P. langeroni, P. balcanicus, S. fallax, S. taizi, S. tiberiadis and S. christophersi. Ecological records of each species and its possible involvement in Leishmania transmission are discussed.

A new method to aid complete lymphadenectomy in radical treatment of cancer of the cervix.

OBJECTIVE: A simple, new and not previously reported method to improve the complete ablation of the pelvic lymph nodes in the surgical treatment of cervical cancer is briefly reported. METHODS: Fourteen patients had been operated upon at Zahrawi Maternity Hospital, Damascus, Syria using radical Wertheim hysterectomy for surgical treatment. Five to 10 days prior to surgery, patients are given intramuscular iron injections that help easy visualization of the lymph nodes during operation. RESULTS: In all the 14 cases treated with this simple pre-operative medication, pelvic lymph nodes were easily identified and completely removed. CONCLUSION: Pre-operative iron injections help in better identification of even the smallest pelvic lymph nodes and improve their complete removal.

Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995: determinants of survival.

In May 1995, an international team characterized and contained an outbreak of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo. This study reports the descriptive features of this outbreak along with a statistical analysis of the outbreak data. Proportional hazards analysis was used to examine the effect of age, phase of the outbreak, and sex on the risk of death, and a conditional probability analysis was used to examine the effectiveness of whole blood transfusion from convalescent patients on survival. Two hundred fifty case-patients (80.7%) died. The main predictor of survival in the proportional hazards model was age. No statistical evidence of a survival benefit of transfusion of blood from convalescent patients was evident after adjusting for age, sex, and the days since onset of symptoms (P = .1713).

Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Epidemiology of rodent bites and prediction of rat infestation in New York City.

The authors examined the epidemiology of rodent bites occurring in New York City from 1986 through 1994 to identify factors contributing to increased probability of rodent bite and rat infestation. City blocks on which a rodent bite case had been reported (n=415) and three control blocks per bite block, matched by borough and randomly selected, were compared according to demographic characteristics obtained from US Census data. Environmental variables were defined using a geographic information system to extract distances to areas potentially providing food or refuge for rats, such as parks. Borough-specific models of bite risk were generated by logistic regression using data collected from 1991 to 1994; risk values were then generated for all city blocks. Field surveys for signs of rat infestation conducted on 31 randomly selected blocks indicated a significant association between degree of infestation and predicted risk. Spatial analyses comparing neighboring blocks showed that blocks with bite cases were significantly clustered. The models based on data from previous years correctly predicted 72 percent of 53 block addresses of rodent bite cases from 1995 as being locations of high or intermediate risk. A combination of geographic and epidemiologic analyses could help investigators identify the spatial occurrence of rat infestation over a large area and might help to focus control activities.

Density estimates of rural dog populations and an assessment of marking methods during a rabies vaccination campaign in the Philippines.

We estimated the population density of dogs by distance sampling and assessed the potential utility of two marking methods for capture-mark-recapture applications following a mass canine rabies-vaccination campaign in Sorsogon Province, the Republic of the Philippines. Thirty villages selected to assess vaccine coverage and for dog surveys were visited 1 to 11 days after the vaccinating team. Measurements of the distance of dogs or groups of dogs from transect lines were obtained in 1088 instances (N = 1278 dogs; mean group size = 1.2). Various functions modelling the probability of detection were fitted to a truncated distribution of distances of dogs from transect lines. A hazard rate model provided the best fit and an overall estimate of dog-population density of 468/km2 (95% confidence interval, 359 to 611). At vaccination, most dogs were marked with either a paint stick or a black plastic collar. Overall, 34.8% of 2167 and 28.5% of 2115 dogs could be accurately identified as wearing a collar or showing a paint mark; 49.1% of the dogs had either mark. Increasing time interval between vaccination-team visit and dog survey and increasing distance from transect line were inversely associated with the probability of observing a paint mark. Probability of observing a collar was positively associated with increasing estimated density of the dog population in a given village and with animals not associated with a house. The data indicate that distance sampling is a relatively simple and adaptable method for estimating dog-population density and is not prone to problems associated with meeting some model assumptions inherent to mark-recapture estimators.

An outbreak of Crimean-Congo hemorrhagic fever in the United Arab Emirates, 1994-1995.

A multi-faceted investigation was conducted in the United Arab Emirates to characterize the epidemiologic and ecologic factors underlying an outbreak of Crimean-Congo hemorrhagic fever (CCHF) noted in November 1994 among abattoir workers. A chart review was conducted among hospitalized suspected cases of viral hemorrhagic fever with onset between January 1994 and March 1995 coupled with serologic testing of available specimens for the presence of virus antigen and IgG and IgM antibodies by ELISA. Livestock handlers and animal skin processors were interviewed and tested for the presence of IgG antibody. Sera from imported and domestic ruminants were examined for antibody for CCHF virus, and ticks collected from these animals were tested with an antigen-capture ELISA. Thirty-five suspected cases of CCHF were identified (case fatality = 62%). Livestock market employees, abattoir workers, and animal skin processors accounted for 16 (57%) of 28 cases with known occupational status. Serologic evidence of past asymptomatic infection was noted in 12 (4%) of 291 livestock and abattoir workers but in none of the controls. Nineteen (7%) of 268 animals were positive for CCHF virus antibodies by ELISA including 12 ruminants from Somalia and Iran and five indigenous camels. One Hyalomma impeltatum and two H. excavatum from Somali cattle and one H. anatolicum from a Somali goat were positive for CCHF virus antigen.

Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus-infected sooty mangabeys.

The extent of zoonotic infections in rural Sierra Leone, where both feral and pet sooty mangabeys harbor divergent members of the human immunodeficiency virus type 2 (HIV-2)-sooty mangabey simian immunodeficiency virus (SIVsm) family, was tested in blood samples collected from 9,309 human subjects in 1993. Using HIV-1- and HIV-2-specific enzyme immunoassays and confirmatory Western blot analysis to test for antibodies to SIVsm-related lentiviruses, we found only nine subjects (0.096%) who tested positive for HIV: seven tested positive for HIV-1 and two tested positive for HIV-2. Compared with other rural West African communities, Sierra Leone displayed the lowest seroprevalence (0.021%) of HIV-2 infection yet reported, much lower than the previously reported seroprevalence in SIVsm-infected feral and household pet sooty mangabeys. Heteroduplex analysis demonstrated that two of the newly found HIV-1 strains belonged to subtype A, the most common HIV-1 subtype in Africa, but this is the first report of subtype A in Sierra Leone. The two HIV-2-infected individuals harbored two distinct HIV-2 strains, designated 93SL1 and 93SL2. Phylogenetic analysis indicated that HIV-2 93SL1 is a member of HIV-2 subtype A, the first strain of this HIV-2 subtype found in Sierra Leone. In contrast, HIV-2 93SL2 belongs to none of the five previously characterized HIV-2 subtypes (A to E) but is a new subtype, herein designated F, having the most divergent transmembrane sequences yet reported for HIV-2. The fact that both of the two most divergent HIV-2 subtypes known, E and F, are rare and found as single occurrences in persons from Sierra Leone may be related to the fact that this small region of West Africa also contains free-living and household pet sooty mangabeys with highly divergent variants of SIVsm. This finding provides support for the hypotheses that new HIV-2 subtypes result from independent cross-species transmission of SIVsm to the human population and that these single-occurrence transmission events had not spread widely into the population by 1993.

Addition of atracurium to lidocaine for intravenous regional anaesthesia.

This study was undertaken to examine the possible clinical advantages of using muscle relaxant with intravenous regional anaesthesia, (IVRA). Forty unpremedicated adult patients undergoing hand surgery were randomly allocated to receive either 40 ml 0.5% lidocaine or 40 ml 0.5% lidocaine with 2 mg of atracurium. The atracurium group of patients had a significantly greater degree of muscle relaxation, easier reduction of fractures, and better operative conditions (P < 0.01). Less pain was also reported during surgery (P < 0.025), and 5 and 15 min after release of the tourniquet (P < 0.01). Clinically, there was no difference in the speed of onset of block between the two groups. It is concluded that the addition of atracurium to lidocaine improves the operating condition during IVRA with less pain during and after surgery.