Characterization of Glucokinases from Pathogenic Free-Living Amoebae.

Infection with pathogenic free-living amoebae, including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (NfGlck) as a potential target for therapeutic intervention, as glucose metabolism is critical for in vitro viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (AcGlck) and B. mandrillaris (BmGlck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, AcGlck and BmGlck have apparent Km values of 472.5 and 41.0 µM, while Homo sapiens Glck (HsGlck) has a value of 310 µM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent Km values of 45.9 µM (AcGlck) and 124 µM (BmGlck) compared to ~8 mM for HsGlck. Additionally, AcGlck and BmGlck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.

Introduction: Coloniality, Educational Leadership, and White Supremacy: The Other Global Pandemic.

In lieu of writing a separate introduction to this special issue, the three guest editors invited the EAQ Editor-In-Chief to join them as a coauthor in their introduction. López, agreed but took a few liberties with the draft that was provided to him by the guest editors. The result is an imagined "conversation" that did not actually take place but is highly probable given the deep admiration and mutual respect the four individuals have for each other both as individuals and as scholars. This introductory conversation situates the theme of the special issue within the larger scope of educational leadership while simultaneously troubling the role of school leaders as agents of Coloniality.

Synthesis of Ring-Fused, N-Substituted 4-Quinolinones Using pKa-Guided, Base-Promoted Annulations with Isatoic Anhydrides: Total Synthesis of Penicinotam.

An anionic annulation strategy employing isatoic anhydrides and a wide assortment of enolizable partners was developed to afford over 80 novel ring-fused, N-substituted 4-quinolinones, an underrepresented privileged template. Multiple factors governing the efficiency of the transformation were determined, resulting in a reliable and tunable synthetic platform applicable for a broad range of substrates with variable deprotonation susceptibility, such as tetramic and tetronic acids, cyclic 1,3-diketones, and cycloalkanones. Application to the synthesis of bioactive, pyrrolizine-fused 4-quinolinone, penicinotam 3, resulted in the most brief and highest yielding total synthesis of the alkaloid in three steps and a 36% overall yield.

Enzymatic and Structural Characterization of the Naegleria fowleri Glucokinase.

Infection with the free-living amoeba Naegleria fowleri leads to life-threatening primary amoebic meningoencephalitis. Efficacious treatment options for these infections are limited, and the mortality rate is very high (∼98%). Parasite metabolism may provide suitable targets for therapeutic design. Like most other organisms, glucose metabolism is critical for parasite viability, being required for growth in culture. The first enzyme required for glucose metabolism is typically a hexokinase (HK), which transfers a phosphate from ATP to glucose. The products of this enzyme are required for both glycolysis and the pentose phosphate pathway. However, the N. fowleri genome lacks an obvious HK homolog and instead harbors a glucokinase (Glck). The N. fowleri Glck (NfGlck) shares limited (25%) amino acid identity with the mammalian host enzyme (Homo sapiens Glck), suggesting that parasite-specific inhibitors with anti-amoeba activity can be generated. Following heterologous expression, NfGlck was found to have a limited hexose substrate range, with the greatest activity observed with glucose. The enzyme had apparent Km values of 42.5 ± 7.3 µM and 141.6 ± 9.9 µM for glucose and ATP, respectively. The NfGlck structure was determined and refined to 2.2-Å resolution, revealing that the enzyme shares greatest structural similarity with the Trypanosoma cruzi Glck. These similarities include binding modes and binding environments for substrates. To identify inhibitors of NfGlck, we screened a small collection of inhibitors of glucose-phosphorylating enzymes and identified several small molecules with 50% inhibitory concentration values of <1 µM that may prove useful as hit chemotypes for further leads and therapeutic development against N. fowleri.

[NOTES ASSISTED ENDOLUMENAL RECTAL RESECTION AND SPECIMEN EXTRACTION WITHOUT RECTAL STUMP OPENING - OUR EXPERIENCE WITH THIS NOVEL TECHNIQUE IN A PORCINE MODEL].

INTRODUCTION: Laparoscopic surgery has long been used for colon and rectal resection, and the laparoscopic-assisted approach has prevailed in surgical practice. While this technique includes the fashioning of an intra-corporeal anastomosis, it still requires an abdominal incision for specimen extraction. Elimination of the abdominal incision and its potential complications has been the motivation for the development of natural orifice specimen extraction (NOSE) techniques. Many of these techniques make use of an open rectal stump, which poses as a potential for intra-abdominal contamination. AIMS: Our group has recently described a novel, NOTES assisted, clean, endoluminal rectal resection utilizing transabdominal and transanal approaches. In this paper we report the combined experience of two study groups: an open approach to the abdominal cavity and a laparoscopic approach to the peritoneal cavity. METHODS: Ten female pigs were used for this research; 5 in a group using an open approach and 5 using a laparoscopic approach for the abdominal part of the procedure. During the procedure, the rectum was mobilized. An end-to-end circular stapler was used to create a recto-rectal intussusception and pull-through (IPT). The specimen was resected and extracted by making a full thickness incision through 2 bowel walls. The stapler was applied, and a recto-rectal anastomosis created. This was allowed to retract into the abdomen. Peritoneal fluid was sampled for bacteria, the pigs were sacrificed immediately after the experiment and necropsy was performed. RESULTS: All 10 pigs underwent an endoluminal rectal resection utilizing the trans-anal IPT technique. The proximal and distal resection margins remained approximated over the shaft of the anvil after bowel resection in all 10 subjects. A 2- to 4-mm resection margin, distal to the ligatures was accomplished consistently in all 10 subjects. No aerobic or anaerobic bacterial growth was observed in any of the peritoneal fluid samples. CONCLUSIONS: Our research demonstrated the feasibility of the described technique in both open and laparoscopic approaches to a clean endoluminal bowel resection and trans-anal specimen extraction without rectal stump opening. The fact that no bacterial growth was found in any of the peritoneal samples supports the initial classification of this novel technique as clean, as opposed to clean contaminated, which classifies all other techniques in use to date.

Unlimited-Length Proctocolectomy Utilizing Sequential Intussusception and Pull-Through: Novel Clean Endolumenal NOTE-Assisted Technique With Transanal Natural Orifice Specimen Extraction Without Rectal Stump Opening in a Porcine Model.

Transanal, hybrid natural orifice translumenal endoscopic surgery (NOTES) and NOTES-assisted natural orifice specimen extraction techniques hold promise as leaders in the field of natural orifice surgery. We report the feasibility of a novel NOTES assisted technique for unlimited length, clean, endolumenal proctocolectomy in a porcine model. This technique is a modification of a transanal intussusception and pull-through procedure recently published by our group. Rectal mobilization was achieved laparoscopically; this was followed by a transanal recto-rectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached laparoscopically to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. To achieve an unlimited-length proctocolectomy, the IPT step was repeated several times prior to bowel resection. This was facilitated by removing the ligature applied in the first step of this procedure. Once sequential IPT established the desired length of bowel to be resected, a second ligature was placed around the rectum approximating the proximal and distal resection margins. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls. The anastomosis was achieved by deploying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. The minimally invasive nature of this evolving technique as well as its aseptic bowel manipulation has the potential to limit the complications associated with abdominal wall incision and surgical site infection.

Synthesis of N-substituted aryl amidines by strong base activation of amines.

We describe an efficient method for the direct preparation of N-substituted aryl amidines from nitriles and primary amines. The protocol employs activation of amines by a strong base and provides greater access to a pharmaceutically relevant functional group. This synthetic approach tolerates deactivated nitriles, nitriles with competing substitution sites, and aryl amines.

Facile Synthesis and Properties of 2-λ(5)-Phosphaquinolines and 2-λ(5)-Phosphaquinolin-2-ones.

Treatment of 2-ethynylanilines with P(OPh)3 gives either 2,2-diphenoxy-2-λ(5)-phosphaquinolines or 2-phenoxy-2-λ(5)-phosphaquinolin-2-ones under transition-metal-free conditions. This reaction offers access to an underexplored heterocycle, which opens up the study of the fundamental nature of the N=P(V) double bond and its potential for delocalization within a cyclic π-electron system. This heterocycle can serve as a carbostyril mimic, with application as a bioisostere for pharmaceuticals based on the 2-quinolinone scaffold. It also holds promise as a new fluorophore, since initial screening reveals quantum yields upwards of 40%, Stokes shifts of 50-150 nm, and emission wavelengths of 380-540 nm. The phosphaquinolin-2-ones possess one of the strongest solution-state dimerization constants for a D-A system (130 M(-1)) owing to the close proximity of a strong acceptor (P=O) and a strong donor (phosphonamidate N-H), which suggests that they might hold promise as new hydrogen-bonding hosts for optoelectronic sensing.

Commercially available trabecular metal ankle interpositional spacer for tibiotalocalcaneal arthrodesis secondary to severe bone loss of the ankle.

Retrograde tibiotalocalcaneal nailing arthrodesis has proved to be a viable salvage procedure; however, extended bone loss around the ankle has been associated with high rates of nonunion and considerable shortening of the hindfoot. We present the surgical technique and the first 2 cases in which a trabecular metal™ interpositional spacer, specifically designed for tibiotalocalcaneal nailing arthrodesis, was used. The spacer can be implanted using either an anterior or a lateral approach. An integrated hole in the spacer allows a retrograde nail to be inserted, which provides excellent primary stability of the construct. Trabecular metal™ is a well-established and well-described material used to supplement deficient bone stock in surgery of the spine, hip, and knee. It has shown excellent incorporation and reduces the need for auto- and allografts. The trabecular metal™ interpositional ankle spacer is the first trabecular metal spacer designed specifically for ankle surgery. Its shape and variable size will make it a valuable tool for reconstructing bone loss in tibiotalocalcaneal nailing arthrodesis.

The Outcome of Local Excision of Rectal Adenomas with High-Grade Dysplasia by Transanal Endoscopic Microsurgery: A Single-Center Experience.

Background: Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods: Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results: Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence (p = 0.03). Conclusions: HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions.

Synthesis and Evaluation of Benzylamine Inhibitors of Neuropathogenic Naegleria fowleri "Brain-Eating" Amoeba.

Current therapy for primary amoebic meningoencephalitis (PAM), a highly lethal brain infection in humans caused by Naegleria fowleri amoeba, is restricted to repurposed drugs with limited efficacy and success. Discovery of an antiamoebic benzylamine scaffold 2 precipitated a medicinal chemistry effort to improve potency, cytotoxicity profile, and drug-like properties. Thirty-four compounds were prepared, leading to compound 28 with significant gains in potency (EC50 = 0.92 µM), solubility, and microsomal stability and a demonstrated absence of cytotoxicity in SH-SY5Y human neuroblastoma cells (CC50 > 20 µM). The compounds demonstrated excellent blood-brain barrier permeability in an in vitro assay, thereby providing a new structural scaffold that inhibits N. fowleri viability and permits the investigation of therapeutic interventions in an understudied neglected disease.

Excision of malignant and pre-malignant rectal lesions by transanal endoscopic microsurgery in patients under 50 years of age.

BACKGROUND: The most common technique for treating benign and early malignant rectal lesions is transanal endoscopic microsurgery (TEM). Local excision is an acceptable technique for high-risk and elderly patients, but there are hardly any data regarding young patients. AIM: To describe TEM outcomes in patients under 50 years of age. METHODS: We collected demographic, clinical, and pathological data from all patients under the age of 50 years who underwent the TEM procedure at Hasharon Rabin Medical Center from January 2005 to December 2018. RESULTS: During the study period, a total of 26 patients under the age of 50 years underwent TEM procedures. Their mean age was 43.3 years. Eleven (42.0%) were male. The mean operative time was 67 min, and the mean tumor size was 2.39 cm, with a mean anal verge distance of 8.50 cm. No major intraoperative or postoperative complications were recorded. The median length of stay was 2 d. Seven (26.9%) lesions were adenomas with low-grade dysplasia, four (15.4%) were high-grade dysplasia adenomas, two were T1 carcinomas (7.8%), and three were T2 carcinomas (11.5%). No residual disease was found following endoscopic polypectomy in two patients (7.8%), but four (15.4%) had other pathologies. Surgical margins were negative in all cases. Local recurrence was detected in one patient 33 mo following surgery. CONCLUSION: Among young adult patients, TEM for benign rectal lesions has excellent outcomes. It may also offer a balance between the efficacy of complete oncologic resection and postoperative quality of life in the treatment of rectal cancer. In some cases, it may be considered an alternative to radical surgery.

Trans-anal endoscopic microsurgery for non- adenomatous rectal lesions.

BACKGROUND: Trans-anal endoscopic microsurgery (TEM) enables a good visualization of the surgical field and is considered the method of choice for excision of adenomas and early T1 rectal cancer. The rectum and retro-rectal space might be the origin of uncommon neoplasms, benign and aggressive, certain require radical trans-abdominal surgery, while others can be treated by a less aggressive approach. In this study we report outcomes in patients undergoing TEM for rare and non-adenomatous rectal and retro-rectal lesions over a period of 11 years. AIM: To report outcomes in patients undergoing TEM for rare and non-adenomatous rectal and retro-rectal lesions over a period of 11 years. METHODS: Between January 2008 to December 2019 a retrospective analysis was completed for all patients who underwent TEM for non-adenomatous rectal lesion or retro-rectal mass in our institution. Patients were discharged once diet was well tolerated and no complications were identified. They were evaluated at 3 wk post operatively, then at 3-mo intervals for the first 2 years and every 6 mo depending on the nature of the final pathology. Clinical examination and rectoscopy were performed during each of the follow-up visits. RESULTS: Out of 198 patients who underwent TEM during the study period, 18 had non-adenomatous rectal or retro-rectal lesions. Mean age was 47 years. The mean size of the lesions was 2.9 mm, with a mean distance from the anal margin of 7.9 cm. Mean surgical time was 97.8 min. There were no intra-operative neither late post-operative complications. Mean length of stay was 2.5 d. Mean patient follow-up duration was 42 mo. CONCLUSION: TEM allows for reduced morbidity given its minimally invasive nature. Surgeons should be familiar with the technique but careful patient selection should be considered. It can be used safely for uncommon rectal and selected retro-rectal lesions without compromising outcomes. We believe that it should be reasonably considered as one of the surgical methods when treating rare lesions.

Rectal Cancer following Local Excision of Rectal Adenomas with Low-Grade Dysplasia-A Multicenter Study.

Purpose: Rectal polyps with low-grade dysplasia (LGD) can be removed by local excision surgery (LE). It is unclear whether these lesions pose a higher risk for recurrence and cancer development and might warrant an early repeat rectal endoscopy. This study aims to assess the rectal cancer rate following local excision of LGD rectal lesions. Methods: A retrospective multicenter study including all patients that underwent LE for rectal polyps over a period of 11 years was conducted. Demographic, clinical, and surgical data of patients with LGD werecollected and analyzed. Results: Out of 274 patients that underwent LE of rectal lesions, 81 (30%) had a pathology of LGD. The mean patient age was 65 ± 11 years, and 52 (64%) were male. The mean distance from the anal verge was 7.2 ± 4.3 cm, and the average lesion was 3.2 ± 1.8 cm. Full thickness resection was achieved in 68 patients (84%), and four (5%) had involved margins for LGD. Nine patients (11%) had local recurrence and developed rectal cancer in an average time interval of 19.3 ± 14.5 months, with seven of them (78%) diagnosed less than two years after the initial LE. Seven of the nine patients were treated with another local excision, whilst one had a low anterior resection, and one was treated with radiation. The mean follow-up time was 25.3 ± 22.4 months. Conclusions: Locally resected rectal polyps with LGD may carry a significant risk of recurring and developing cancer within two years. This data suggests patients should have a closer surveillance protocol in place.

Assessing the interaction of land cover/land use dynamics, climate extremes and food systems in Uganda.

Rainfed agriculture is Uganda's mainstay across the different regions of its territory. Farmland area has been reported to increase despite agriculture's vulnerability to climate variations. This great interplay among land-use dynamics, climate extremes, and food systems is, however, understudied. The current research, therefore, explores this interaction at both national and regional scales for the period between 2001 and 2017. Following an approach that employs remote sensing datasets on Net Primary Productivity (NPP), land cover types, drought indices, and climate variables, i.e. precipitation, temperature, and evapotranspiration, impacts of climate extremes and land cover changes on food production have been analysed. Similarly, the performance of ten major crops in Uganda over the last 6 decades has been detected using the Regime Shift technique. Key findings, thereof, indicate that NPP in farmlands is sensitive to climate variability, and this sensitivity varies spatially among the regions. Forests and permanent wetlands have been massively changed into farmlands, hence, moving a step forward into offsetting food insecurity but a step backward in preserving ecosystem services, espcially mitigating climate change. Furthermore, the noticeable increase in the total production of the major crops in Uganda seems to be derived mainly by the increase in area harvested affirming the step towards food security. However, the influences, thereof, may aggravate climate change impacts especially through reversing carbon sinks into carbon sources. This reversal could impact the crop yields further. Contrastingly, results from some crops illustrate the potential to increase crop production without necessarily expanding the cropland area. Therefore, Uganda may, instead, consider exploiting the maximum yield potential of crops through, for instance, augmenting rainfed agriculture with irrigation and enforcing effective policies rather than expanding farmland area. These findings collectively contribute further to our understanding of the importance of policies that ensure food security but at the same time preserve a healthy environment.

Case Report: Delayed Primary Wound Closure After Extensive Abdominal Wall Resection for Infection and Malignancy Using TopClosure®.

The closure of a massive abdominal wall defect is illustrated using a novel dynamic closure technique - the TopClosure® tension relief system. This system attaches to the abdominal wall immediately after laparotomy and allows for early approximation of the skin, avoiding an open abdomen and the complications associated with this. The technique in this case was employed after extensive resection of the abdominal wall for infected skin metastases of colonic adenocarcinoma and circumvented post-operative ventilation and open abdomen. Early recovery after such extensive surgery is important in terms of patient morbidity and mortality. In this case, primary surgery may not have been an acceptable risk to undertake without the option of Top Closure of the abdomen. We illustrate the technique of abdominal wall closure through a series of images of the procedure.

Novel Transgastric Endoluminal Segmental Esophagectomy and Primary Anastomosis Technique: A Hybrid Transgastric Thoracoscopic Esophagectomy for the Treatment of High Grade Dysplasia and Early Esophageal Cancer in a Porcine Ex vivo Model.

Multiple modalities are currently employed in the treatment of high grade dysplasia and early esophageal carcinoma. While they are the subject of ongoing investigation, surgery remains the definitive modality for oncological resection. Esophagectomy, however, is traditionally a challenging surgical procedure and carries a significant incidence of morbidity and mortality. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are considerably less invasive alternatives to esophagectomy in the diagnosis and treatment of high grade dysplasia, early esophageal squamous cell carcinoma and adenocarcinoma. However, many early esophageal cancer patients, with favorable histology, who could benefit from endoscopic resection, are referred for formal esophagectomy due to lesion characteristics such as unfavorable lesion morphology or recurrence after previous endoscopic resection. In this study we present a novel, hybrid thoracoscopic transgastric endoluminal segmental esophagectomy with primary anastomosis for the potential treatment of high grade dysplasia and early esophageal cancer in a porcine ex vivo model as a proposed bridge between endoscopic resection and the relatively high mortality and morbidity formal esophagectomy procedure. The novel technique consists of thoracoscopic esophageal mobilization in addition to transgastric endoluminal segmental esophagectomy and anastomosis utilizing a standard circular stapler. The technique was found feasible in all experimental subjects. The minimally invasive nature of this novel procedure as well as the utility of basic surgical equipment and surgical skill is an important attribute of this method and can potentially make it a treatment option for many patients who would otherwise be referred for a formal esophagectomy.

Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (Z)-Benzamidines.

An expedient route to enantiopure, diastereomeric pyrrolopyrazinoquinazolinones was developed following the discovery of a domino quinazolinone rearrangement-intramolecular cyclization of N-H benzamidines. A Ugi-Mumm-Staudinger sequence employing an optically pure proline derivative gave quinazolinones that, upon N-Boc deprotection, rearranged to tautomeric Z-benzamidines. Subsequent spontaneous cyclization afforded 15 diastereomeric pyrazinoquinazolinone pairs in up to 83% overall yield and 89:11 d.r which were separated easily via routine chromatographic purification-the only one required in the entire process.

Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii.

Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.

Spatio-temporal variations in climate, primary productivity and efficiency of water and carbon use of the land cover types in Sudan and Ethiopia.

The impact of climate variability on the Net Primary Productivity (NPP) of different land cover types and the reaction of NPP to drought conditions are still unclear, especially in Sub-Saharan Africa. This research utilizes public-domain data for the period 2000 through 2013 to analyze these aspects for several land cover types in Sudan and Ethiopia, as examples of data-scarce countries. Spatio-temporal variation in NPP, water use efficiency (WUE) and carbon use efficiency (CUE) for several land covers were correlated with variations in precipitation, temperature and drought at different time scales, i.e. 1, 3, 6 and 12months using Standardized Precipitation Evapotranspiration Index (SPEI) datasets. WUE and CUE were estimated as the ratios of NPP to actual evapotranspiration and NPP to Gross Primary Productivity (GPP), respectively. Results of this study revealed that NPP, WUE and CUE of the different land cover types in Ethiopia have higher magnitudes than their counterparts in Sudan. Moreover, they exhibit higher sensitivity to drought and variation in precipitation. Whereas savannah represents the most sensitive land cover to drought, croplands and permanent wetlands are the least sensitive ones. The inter-annual variation in NPP, WUE and CUE in Ethiopia is likely to be driven by a drought of time scale of three months. No statistically significant correlation was found for Sudan between the inter-annual variations in these indicators with drought at any of the time scales considered in the study. Our findings are useful from the view point of both food security for a growing population and mitigation to climate change as discussed in the present study.