Leveraging differentiated HIV service delivery to expand tuberculosis preventive treatment: a call to action.

Tuberculosis (TB) is the leading cause of death among people living with human immunodeficiency virus (PLHIV), and sub-Saharan Africa has a particularly heavy burden of HIV-associated TB. Although effective TB preventive treatment (TPT) has been available for decades and shorter regimens are newly available in some settings, TPT coverage among PLHIV is suboptimal, leading to preventable illness and death. In 2018, the United Nations High-Level Meeting on Ending Tuberculosis called for ambitious new targets for TPT coverage among PLHIV and many countries in sub-Saharan Africa have redoubled their efforts to take TPT to scale. Importantly, however, this push to expand TPT among PLHIV is taking place in the context of a changing HIV treatment delivery landscape. Countries in sub-Saharan Africa are at the forefront of innovative changes in HIV program design, including a shift towards less-intensive differentiated service delivery (DSD) models for stable patients doing well on antiretroviral therapy. Understanding the opportunities and challenges that DSD presents for TB diagnosis, prevention and linkage to care among PLHIV will be critical to success.

Osmoconditioning prevents the onset of microtubular cytoskeleton and activation of cell cycle and is detrimental for germination of Jatropha curcas L. seeds.

Jatropha curcas is an oilseed crop renowned for its tolerance to a diverse range of environmental stresses. In Brazil, this species is grown in semiarid regions where crop establishment requires a better understanding of the mechanisms underlying appropriate seed, seedling and plant behaviour under water restriction conditions. In this context, the objective of this study was to investigate the physiological and cytological profiles of J. curcas seeds in response to imbibition in water (control) and in polyethylene glycol solution (osmoticum). Seed germinability and reactivation of cell cycle events were assessed by means of different germination parameters and immunohistochemical detection of tubulin and microtubules, i.e. tubulin accumulation and microtubular cytoskeleton configurations in water imbibed seeds (control) and in seeds imbibed in the osmoticum. Immunohistochemical analysis revealed increasing accumulation of tubulin and appearance of microtubular cytoskeleton in seed embryo radicles imbibed in water from 48 h onwards. Mitotic microtubules were only visible in seeds imbibed in water, after radicle protrusion, as an indication of cell cycle reactivation and cell proliferation, with subsequent root development. Imbibition in osmoticum prevented accumulation of microtubules, i.e. activation of cell cycle, therefore germination could not be resumed. Osmoconditioned seeds were able to survive re-drying and could resume germination after re-imbibition in water, however, with lower germination performance, possibly due to acquisition of secondary dormancy. This study provides important insights into understanding of the physiological aspects of J. curcas seed germination in response to water restriction conditions.

Palliative surgical intervention in metastatic colorectal carcinoma: a prospective analysis of quality of life.

AIM: Quality of life (QOL) was assessed after palliative surgery for incurable metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with incurable metastatic CRC who were offered elective palliative surgical intervention were included. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL at baseline and at 3 and 6 months after surgery. Generalized estimating equations were used to estimate the mean change in the QOL score from baseline. RESULTS: Twenty-four patients formed the study group. Sixteen underwent resection of the primary tumour and eight had a proximal diversion or bypass. The Global Health (GH) score and Social Functioning (SF) score improved at 3 and 6 months after intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months) and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012). Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable metastatic CRC, surgery improved QOL.

Indução, caracterização bioquímica e ultra-estrutural de calos de aroeira-do-sertão (Myracrodruon urundeuva Fr. All. ) / Induction, biochemical and ultrastructural characterization of the callus of "aroeira-do-sertão" (Myracrodruon urundeuva Fr. All. )

A aroeira-do-sertão (Myracrodruon urundeuva Fr. All.) é espécie arbórea que apresenta grande valor econômico devido às propriedades químicas da casca com elevado teor de taninos. Em decorrência da exploração predatória encontra-se inserida na lista oficial de espécies da flora brasileira ameaçadas de extinção na categoria vulnerável. A micropropagação vem sendo colocada como importante forma de multiplicação dessa espécie, na busca de alternativa para a exploração sustentável. Este trabalho foi realizado com o objetivo de induzir calos a partir de segmentos foliares usando 2,4-D e caracterizá-los quanto aos aspectos morfológicos e bioquímicos. Os resultados obtidos indicam que é possível induzir calos a partir de segmentos foliares de aroeira-do-sertão utilizando-se 2,4-diclorofenoxiacético (2,4-D). Os calos obtidos foram compactos e não-embriogênicos, apresentando valores médios de 43,32 mg g-1 de açúcares solúveis totais; 23,62 mg g-1 de açúcares redutores; 3,157 mg g-1 de proteína total; 3,147 mg g-1 de aminoácidos livres e 0,914 mg g-1 de compostos fenólicos totais na matéria fresca.

"Aroeira-do-sertão" (Myracrodruon urundeuva Fr. All.) is a tree species that has great economic value due to the chemical properties of its bark, which has high tannin content. On account of the predatory exploitation it has been placed in the official list of threatened species of the Brazilian flora, in the vulnerable category. Micropropagation has been considered an important form of multiplication of this species in the search for an alternative for its sustainable exploitation. This study was conducted with the aim of inducing callus from leaf segments using 2,4-D and characterizing them according to their morphological and biochemical aspects. The obtained results indicate that it is possible to induce callus from leaf segments of M. urundeuva using 2,4-dichlorophenoxyacetic (2,4-D). The obtained calluses were compact and non-embryogenic, with average values of 43.32 mg g-1 total soluble sugars, 23.62 mg g-1 reducing sugars, 3.157 mg g-1 total protein, 3.147 mg g-1 free-form amino acids and 0.914 mg g-1 phenolic compounds in the fresh matter.

Atividade antibacteriana in vitro de extratos de Rhizophora mangle L. / In vitro antibacterial activity of Rhizophora mangle L. extracts

Ensaios para avaliar o potencial antibacteriano de Rhizophora mangle (mangue-vermelho), coletada no município de Conde, Bahia, foram realizados com cepas bacterianas Gram-positivas (Staphylococcus aureus ATCC 6538 e Micrococcus luteus ATCC 9341) e Gram-negativas (Echerichia coli ATCC 10536, Salmonella Cholerea-suis 10708, Klebsiela pneumoniae ATCC 700603 e Pseudomonas aeruginosa ATCC 15442). A atividade antibacteriana foi avaliada pelos métodos de difusão em disco e concentração inibitória mínima (CIM), e os resultados analisados estatisticamente. Os resultados do ensaio de difusão em disco mostraram diferença significativa quanto à sensibilidade dos micro-organismos frente aos extratos testados (p<0,05). A CIM do extrato da folha (313 µg mL-1) apresentou o melhor desempenho para inibir o crescimento das cepas Gram-positivas, enquanto o extrato da casca foi mais eficaz para as cepas Gram-negativas. De acordo com os dados levantados por este estudo, R. mangle apresentou propriedade antibacteriana para cepas Gram-positivas e Gram-negativas, podendo tornar-se alternativa terapêutica tanto para o uso popular quanto para a indústria farmacêutica.

Assays to evaluate the antibacterial potential of Rhizophora mangle (red mangrove), sampled at Conde Municipality, Bahia State, Brazil, were performed against Gram-positive (Staphylococcus aureus ATCC 6538 and Micrococcus luteus ATCC 9341) and Gram-negative (Echerichia coli ATCC 10536, Salmonella Cholerea-suis 10708, Klebsiela pneumoniae ATCC 700603 and Pseudomonas aeruginosa ATCC 15442) bacteria. Antibacterial activity was evaluated by disc diffusion and minimal inhibitory concentration (MIC) and results were statistically analyzed. The results of disc diffusion assay showed a significant difference as to the sensitivity of microorganisms against the tested extracts (p<0.05). The MIC of leaf extract (313 µg mL-1) indicated the best performance to inhibit the growth of Gram-positive strains, while bark extract had a better efficacy against Gram-negative strains. Based on the presented data, R. mangle showed antibacterial properties against both Gram-positive and Gram-negative strains and can be used as an alternative therapy for popular use or for the pharmaceutical industry.

Percutaneous dilatational tracheostomy in a community hospital setting.

BACKGROUND: Over the past 15 years, many large university hospitals have reported their experience with percutaneous dilatational tracheostomy (PDT). The purposes of this study are to evaluate the safety of PDT in a non-university hospital setting and to compare our results with those published in the literature. METHODS: The study was done by retrospective chart review. RESULTS: Over a 6-year period, 300 PDTs were done in two community hospitals in Tyler, Texas. There was one death and 12 complications. Comparison of our results and those reported in five recently published articles in the literature showed no significant difference in mortality rate, pneumothorax, bleeding, paratracheal placement, dislodgement, or cellulitis. There was a trend toward a significantly lower incidence of paratracheal placement using bronchoscopic guidance. CONCLUSION: Bedside PDT with bronchoscopic guidance can be safely done in a community hospital setting.

Incidence of tracheal stenosis and other late complications after percutaneous tracheostomy.

OBJECTIVE: To determine the incidence of tracheal stenosis, voice and breathing changes, and stomal complications after percutaneous dilatational tracheostomy (PDT). METHODS: From December 1992 through June 1999, 420 critically ill patients underwent 422 PDTs. There were 340 (81%) long-term survivors, 100 (29%) of whom were interviewed and offered further evaluation by fiberoptic laryngotracheoscopy (FOL) and tracheal computed tomography (CT). Tracheal stenosis was defined as more than 10% tracheal narrowing on transaxial sections or coronal and sagittal reconstruction views. Forty-eight patients agreed to CT evaluation; 38 patients also underwent FOL. CT and FOL evaluations occurred at 30 +/- 25 (mean +/- standard deviation) months after PDT. RESULTS: Twenty-seven (27%) patients reported voice changes and 2 (2%) reported persistent severe hoarseness. Vocal cord abnormalities occurred in 4/38 (11%) patients, laryngeal granuloma in 1 (3%) patient, focal tracheal mucosal erythema in 2 (5%) patients, and severe tracheomalacia/stenosis in 1 (2.6%) patient. CT identified mild (11-25%) stenosis in 10 (21%) asymptomatic patients, moderate (26-50%) stenosis in 4 (8.3%) patients, 2 who were symptomatic, and severe (>50%) stenosis in 1 (2%) symptomatic patient. Ten patients (10%) reported persistent respiratory problems after tracheal decannulation, but only four agreed to be studied. Two patients had moderate stenosis, and one had severe stenosis. One patient's CT scan was normal. No long-term stomal complications were identified or reported. CONCLUSIONS: Subjective voice changes and tracheal abnormalities are common after endotracheal intubation followed by PDT. Long-term follow-up of critically ill patients identified a 31% rate of more than 10% tracheal stenosis after PDT. Symptomatic stenosis manifested by subjective respiratory symptoms after decannulation was found in 3 of 48 (6%) patients.

The safety of prolonging the use of central venous catheters: a prospective analysis of the effects of using antiseptic-bonded catheters with daily site care.

OBJECTIVE: To determine rates of catheter colonization and catheter-related bloodstream infection (CRBSI) when antiseptic-bonded central venous catheters (CVCs) and standardized daily site care are used with no predetermined interval for removal. DESIGN: Prospective observational study. SETTING: Two major trauma centers. PATIENTS: All trauma patients admitted to two major trauma centers that received a CVC from May 1996 through May 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Catheters were semiquantitatively cultured to identify bacterial colonization and CRBSI. Monitored variables included total catheter days, anatomical site of catheter insertion, and area in hospital of catheter insertion. CVC tips and intracutaneous segments were semiquantitatively cultured. A total of 460 (92%) of 501 catheters placed in 324 trauma patients were evaluable, representing 95.5% of all catheter days during the study period. Rates of catheter colonization and CRBSI were 5% (5/1000 catheter days) and 1.5% (1.511000 catheter days), respectively. Subclavian catheters were in place longer than femoral or internal jugular catheters (p < .0001), but the colonization rate was significantly lower (p = .03; relative risk, 0.34; 95% confidence interval, 0.15-0.77). No differences in CRBSI rates among anatomical sites or between catheters used < or =14 days and those used >14 days were identified. CONCLUSION: Femoral and internal jugular antiseptic-bonded CVCs develop bacterial colonization earlier than subclavian CVCs. Subclavian antiseptic-bonded CVCs combined with standardized daily site care may be safely used >14 days in trauma patients.

Mechanisms and patterns of injuries related to large animals.

BACKGROUND: Injuries from encounters with large animals represent a significant health risk for rural communities. We evaluated our regional trauma centers' experience with large-animal injuries to determine whether certain mechanisms and patterns of injury predicted either major head/craniofacial or torso (chest/abdomen/pelvis) trauma. METHODS: The hospital courses of 145 patients with injuries related to large animals were reviewed retrospectively to determine patterns of injury, specific injury mechanisms, species-specific injuries, and predictors of multiple body region trauma. RESULTS: Seventy-nine patients (55%) were injured by horses, 47 patients (32%) by bulls, 16 patients (11%) by cows, and 3 patients (2%) by wild animal attacks. The predominant species-specific mechanisms of injury were falls (horses), tramplings (bulls), and kicks (cows). Brain/craniofacial injuries were most common from horse-related encounters (32%), whereas bull and cow encounters usually resulted in torso injuries (45% and 56%, respectively). Multiple body region injuries occurred in 32% of patients. Fractures of the upper extremities were more often associated with torso and head/craniofacial injuries (48%) than lower extremity injuries (17%) (p = 0.02). CONCLUSION: Large animal injuries frequently involve multiple body regions with species-specific mechanisms. Upper extremity injuries are associated with a significantly higher percentage of torso and head/craniofacial injuries, which may have implications for field triage.

Homeostasis in mice with genetically decreased angiotensinogen is primarily by an increased number of renin-producing cells.

Here we investigate the biochemical, molecular, and cellular changes directed toward blood pressure homeostasis that occur in the endocrine branch of the renin-angiotensin system of mice having one angiotensinogen gene inactivated. No compensatory up-regulation of the remaining normal allele occurs in the liver, the main tissue of angiotensinogen synthesis. No significant changes occur in expression of the genes coding for the angiotensin converting enzyme or the major pressor-mediating receptor for angiotensin, but plasma renin concentration in the mice having only one copy of the angiotensinogen gene is greater than twice wild-type. This increase is mediated primarily by a modest increase in the proportion of renal glomeruli producing renin in their juxtaglomerular apparatus and by four times wild-type numbers of renin-producing cells along afferent arterioles of the glomeruli rather than by up-regulating renin production in cells already committed to its synthesis.

Structure of the oligonucleotide d(CGTATATACG) as a site-specific complex with nickel ions.

In this paper we explore the application of Ni2+to the crystallization of oligonucleotides. We have determined in this way the structure of a fully alternating (Y-R) decanucleotide d(CGTATATACG) by single crystal X-ray diffraction. This is the first oligonucleotide crystal structure with an alternating 5'-(TA)3-3' central part. Alternating oligonucleotides have a particular interest since they often have a unique structure. In this case the general conformation is B-like with an alternating twist and an end-to-end interaction which involves terminal guanines. The crystal belongs to space group P41212 with a = b = 52.46, c = 101.49 A. This packing imposes a 90 degrees crossing of the symmetry related helices. This is a new way of packing for decamers. The oligonucleotide structure is characterized by the specific association with seven nickel ions, involving the N7 atom of every guanine. One of the Ni2+ions is shared between two guanines of symmetry related molecules. Until now no oligonucleotide has been crystallized in the presence of this metal ion. A novel C.A.T triplet structure has also been tentatively identified.

Structure of the d(CGCCCGCGGGCG) dodecamer: a kinked A-DNA molecule showing some B-DNA features.

We have determined the structure of the dodecamer duplex d(CGCCCGCGGGCG)2. A careful use of the molecular replacement programme AMoRe has been essential in order to solve the structure. This dodecamer shows a unique conformation, quite different from all the previously studied oligonucleotide duplexes: the central octamer has an A conformation, but with a sharp 65 degrees kink in the centre; the terminal base-steps have a B-like conformation; the major groove is completely closed in the centre, a hollow molecule is thus found. The results obtained confirm the high degree of variability of DNA structure. A new type of kink and an intermediate A/B double-helical conformation have been found. Such intermediate conformation differs from those described in DNA polymerase complexes.

Structural variability of A-DNA in crystals of the octamer d(pCpCpCpGpCpGpGpG)

We have determined the structure of the synthetic DNA octamer d(pCpCpCpGpCpGpGpG) in five different crystal forms by single crystal X-ray diffraction. One crystal belongs to the space group P4(3)2(1)2 with a = b = 41.77, c = 25.15 A, whereas all others have the space group P2(1)2(1)2(1) with progressively decreasing unit cell volumes. In all crystals the octamer forms duplexes of A-DNA and all crystals display a similar packing mode, typical for A-DNA. The structure of the duplex varies from loose to very compact when going from one crystal form to another. The most compact form exhibits a volume of 995 A3 per base pair. Such a high density has never been found in A-DNA, being more characteristic of Z-DNA crystals. A comparison of the most with the least compact forms gives a RMS value of 1.7 A, with the distance between the phosphate centers through the major groove being almost twice shorter in the compact form. The phosphate-phosphate separation across the major groove in the compact form is extremely small, 0.7 A. The helical parameters also vary significantly in the various crystal forms. Differences in the helical twist can reach 13 degrees in the same step of the octamer in different crystal forms. The results prove that A-DNA is structurally very variable and demonstrate that the local structure of the same DNA fragment can strongly depend on the crystal environment.

[Multivariate analysis of graft survival prognostic factors in renal transplantation]. / Análisis multivariado de los factores pronósticos en la supervivencia del injerto en el trasplante renal.

OBJECTIVE: The aim of this paper is to identify the variables that could be of interest in the outcome of a series of cadaveric kidney transplantation performed at the University Hospital, Navarra School of Medicine, by means of multifactorial and multivariate statistical analyses. METHOD: We analyzed 307 cadaveric kidney transplantation performed since 1976 at the University Hospital, School of Medicine, University of Navarra. Two series are included: the historical and the actual. The former did not include cyclosporine A in the immunosuppressor protocol. RESULTS: The first step was to compare survival in both series. The cyclosporine A series had a better survival, which was statistically significant (p < 0.0001). The prognostic factors in both series were also analyzed. The influence of the different variables were studied in the survival distribution. The worse prognostic variables of the historical group on allograft survival were donor's age (particularly between 20 and 50 years old), delayed graft function, serum creatinine level greater than 2.5 mg/dl at the first month following transplantation, general surgical complications, and vascular and other complications. In the actual group, the allografts with the worst survival were in those that received 4-10 pre-transplant blood transfusions, those with more that 2 HLA-DR mismatches, the hyperimmunized receptors with a level of pre-formed cytotoxic antibodies greater than 50%, those who rejected the allograft in the initial post-transplant period, those with a serum creatinine level greater than 2.5 mg/dl and those who presented surgical complications in general and urinary and vascular complications in particular. CONCLUSIONS: The multivariate analysis reveals that the prognostic factors of the historical group were delayed graft function, surgical complications, HLA A+B mismatches and the donor's age. In the actual group, the factors were receptor's age, surgical complications, large ischemia time, peak reactive antibody and number of rejections.

Thoracic BB injuries in pediatric patients.

Penetrating thoracic injury from BB shot remains an innocuous event in most patients, but factors including location, proximity, gun type, and patient weight may identify groups at risk. The following cases demonstrate morbidity and mortality in two patients, and this experience may suggest the need for reassessment of this injury.

[Multivariate analysis of the impact of surgical complications in renal transplant]. / Análisis multivariado del impacto de las complicaciones quirúrgicas en el trasplante renal.

We analyzed 307 cadaver kidney transplantations performed since 1976 at the University Hospital of the University of Navarra. Two series, the historical and the current one, are presented. In the former, cyclosporine A was not included in the immunosuppressor protocol. The surgical complications were evaluated in both series and their influence on the survival of the allograft. The current series showed a significant decrease in surgical complications. Allograft survival in the historical series was influenced by surgical complications in general, and vascular and other complications in particular. The current series was influenced by surgical complications in general, and urinary and vascular complications in particular. The multivariate analysis showed that surgical complications were one of the most important prognostic factor in both series.

Transesophageal echocardiography for diagnosing aortic injury: a case report and summary of current imaging techniques.

Early diagnosis and rapid treatment of lethal aortic injuries associated with blunt trauma remain a challenge for trauma surgeons. The following case demonstrates the use of transesophageal echocardiography for definitive diagnosis of an aortic injury from blunt trauma. A summary of current diagnostic modalities is also presented.

[Pure squamous carcinoma of the ureter. Review of a case]. / Carcinoma escamoso puro de uréter. Revisión de un caso.

We report a case of squamous cell carcinoma of the ureter with periureteral infiltration. Three years following radical surgery, no evidence of tumor progression has been observed. Only 1% to 1.6% of urothelial tumors of the upper urinary tract are purely squamous cell tumors. This tumor type carries a poor prognosis. Currently, the best results can be achieved by early diagnosis and radical surgery.

[Vascular complications in 237 recipients of renal transplant from cadaver]. / Complicaciones vasculares en 237 receptores de trasplante renal de cadáver.

Between July 1976 and June 1990, 244 transplantations were performed. Of the 237 patients monitored, 13 (5.4%) had vascular complications: 10 (77%) renal artery stenosis, 1 (7.7%) primitive iliac artery stenosis, 1(7.7%) renal artery thrombosis, 1 (7.7%) renal vein thrombosis. Six patients underwent surgery (Angioplasty was performed in three patients, re-anastomosis to the common iliac artery in one, by-pass of saphenous vein in another one, while in the last one it was tried a release of the vascular pediculus). Management with drugs was possible in one case. At present, 11 of the 13 patients are still alive and three of the grafts remain functional after a mean follow-up time of 83 months. According to a univariate study, the influential factors in the development of vascular complications are, the identity of Locus A, the type of extraction in Locus B, the length of cold ischaemia, the type of vascular anastomosis and the number of previous rejections. The factors with maximal influence in the development of complications are the type of vascular suture (with or without patch) and the number of previous rejections (according to a study of log regression models). The study demonstrates the significant influence vascular complications have on the graft's durability (p = 0.005).